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Neurochemistry and behaviour
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Members
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Main topics
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Research at the Rodent Behavioural Research Unit:
The Rodent Behavioural Research Unit at the Laboratory of Neurochemistry & Behaviour holds a considerable expertise in the field of behavioural phenotyping of (transgenic) rodent models for human neurological conditions. Behavioural phenotyping is crucially based upon test batteries of behavioural paradigms assessing different brain and behaviour functions. The Research Unit is fully equipped for behavioural observations in rodents (mice and rats), including the evaluation of pharmacological interventions in specific models, as well as correlations between behavioural alterations and underlying disease mechanisms. The behavioural observation ranges from evaluation of simple reflexes to the systematic registration of complex learned responses as studied in the Morris water maze. Besides various levels of learning and memory performance, a test battery may include assessments of motor performance, equilibrium and coordination, circadian rhythms and exploration, anxiety and fear. The research unit has moreover ample experience in behavioural observations related to isolation-induced aggression, male sexual behaviour, depression-related symptoms, vision and olfaction, ingestive behaviour, and epilepsy. In addition, a complete setup for in vivo electrophysiological recordings in rodents is available.
The following research topics are currently under investigation:
- Behavioural phenotyping of transgenic models for Alzheimer''s disease and related disorders;
- Pharmacological modulations of cognitive and BPSD-related behavioural alterations in the transgenic APP23 mouse model for Alzheimer''s disease;
- Functional peptidomics: study of the behavioural effects of newly discovered peptides.
- Correlation between behavioural deficits and underlying pathophysiological mechanisms in transgenic models for Alzheimer''s disease;
Methods:
Behavioural analyses in rodents using various paradigms employing automated recording systems (Ethovision and custom made) and/or experimenter-based observations;
Acute or chronic administration of compounds
Follow-up breeding colony APP23 mice
Genotyping newborns in breeding colony employing:
- DNA extraction
- PCR
- agarose gel electrophoresis
Research: Biomarkers for (early) dementia diagnosis
The diagnosis of Alzheimer''s disease (AD) is still based on clinical exclusion criteria and the required diagnostic work-up is time consuming and expensive, at best resulting in a diagnosis of probable AD. Average sensitivity and specificity values of respectively 81% and 70% were achieved for a clinical diagnosis of probable AD. Most studies evaluating accuracy rates are, however, based on follow-up periods of several years and have been performed in specialised clinical centres. A much lower diagnostic accuracy can be expected in the earliest stages of the disease and when the diagnostic work-up is performed in non-specialised centres. Low average specificity levels of 48% for clinical diagnosis of possible AD reflect the overlap of clinical profiles between AD and non-AD dementias. Should diagnostic errors occur, they most likely involve one of the other primary dementias, mixed pathologies that include a vascular component, or uncertainties associated with early diagnosis.
A promising approach to increase diagnostic accuracy is the use of biochemical markers (biomarkers) present in easily accessible body fluids like serum, plasma or cerebrospinal fluid (CSF). Within the Reference Centre for Biological Markers of Memory Disorders, we contribute to the development and characterisation of biomarkers, meanwhile developing and validating biomarkers-based diagnostic models that can easily be applied in routine clinical diagnosis. Indeed, several studies have confirmed the relevance of total tau-protein (T-tau) and ß-amyloid peptide (Aß1-42) in the pathogenic processes associated with dementias of neurodegenerative origin. The combined assessment of CSF Aß1-42, T-tau, and tau phosphorylated at threonine 181 (P-tau181P) levels is routinely performed for clinical diagnostic and research purposes.
Recently, we have shown the value of biomarkers in (differential) dementia diagnosis, using the gold standard (pathological diagnosis) as a reference. New models have been developed, enabling the use of the different biomarkers in an optimal algorithm defined by the clinical need. These models show promising sensitivity and specificity. Diagnostic accuracy based on a biomarker model using CSF levels of Aß1-42 and P-tau181P (82.7%) is comparable to diagnostic accuracy strictly applying clinical diagnostic criteria (81.6%), and can help establishing a correct diagnosis in case of doubtful clinical diagnoses. Moreover, biomarkers and biomarker-based diagnostic models are of help for identifying mild cognitive impairment (MCI) patients at risk for conversion to dementia.
Methods:
- Clinical and behavioural observation of dementia patients
- ELISA
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Website
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http://www.bornbunge.be/Home/index_en.shtml
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Projects
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Show the projects of this research team - European Medical Information Framework (EMIF). 01/01/2013 - 31/12/2017
| Abstract | EMIF plans to address the logistical challenges of developing a sustainable and scalable information framework which has the potential to access data on a scale and at a level of detail not currently available which will completely re-shape the way researchers currently approach key scientific questions and also to open avenues of research that so far have been out of reach. The current project will focus on two such research questions to provide focus and some guidance for the framework development:
1) Determination of protective and precipitating factors for conversion from pre-dementia cognitive dysfunction to dementia in general as well as conversion from prodromal Alzheimer''s disease to typical or atypical Alzheimer''s disease. Determine individual susceptibility as well as precipitating factors that cause very elderly patients to convert from biomarker-positive pre-symptomatic stage (asymptomatic at-risk stage) to prodromal, typical or atypical Alzheimer''s disease.
2) The discovery of predictors of the metabolic complications of adult and paediatric obesity, which shall lead to innovative diagnostic tests, pave the way to novel therapeutics targeted to high-risk individuals, and provide the infrastructure to select individuals for such targeted pharmacological interventions. | | Duration | 01/01/2013 - 31/12/2017 | | Researcher(s) | | | Research Team(s) | |
- Biochemical markers for improved diagnostic discrimination of Alzheimer's disease from dementia with Lewy bodies. 01/01/2013 - 31/12/2015
| Abstract | This project aims to investigate biochemical markers for dementia with Lewy bodies aiming at improved clinical diagnosis of this neurological disorder that is often misdiagnosed as Alzheimer''s disease. This research project aims at improving the AD versus DLB differential dementia diagnosis, combining both existing and new biomarkers:
Neurodegenerative dementias are characterized by changes in the brain that include aggregation and deposition of proteins. Biochemical markers (biomarkers) that reflect these neuropathological changes have potential diagnostic value. Some biomarkers have proven their diagnostic value and are able to discriminate Alzheimer''s disease (AD) from healthy controls and patients with depression or other psychiatric disorders. However, given the overlap in clinical symptoms, pathology and pathophysiology, the discrimination of AD from dementia with Lewy bodies (DLB) remains a clinically relevant but unsolved issue. A correct and early AD diagnosis will be of great importance once disease-modifying drugs for AD will become available as these (potentially toxic) drugs will probably be not effective for other types of dementia.
This research will focus on biomarkers in cerebrospinal fluid (CSF) that reflect the neuropathology and thus with potential diagnostic value for discriminating AD from DLB. The combination of different biomarkers in clinically and pathologically well-characterized patient groups makes this research valuable and is clinically relevant as probably only the combination of markers can achieve more accurate results to discriminate DLB from AD. This research will not only improve diagnosing AD and DLB but will also provide new insights in the pathophysiology of dementia. | | Duration | 01/01/2013 - 31/12/2015 | | Researcher(s) | | | Research Team(s) | |
- CSF biomarkers for AD diagnosis: standardization of clinical protocols. 01/01/2013 - 31/12/2014
| Abstract | Diagnostic tools that confirm the diagnosis of Alzheimer''s disease (AD) rather than exclude all other possible causes, could increase diagnostic certainty. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which are made up of ß-amyloid and hyperphosphorylated tau, respectively. As the brain is in direct contact with the cerebrospinal fluid (CSF) and the flow of proteins to and from the CSF is restricted by the blood-CSF barrier, biochemical changes that reflect pathophysiological processes in the brain are therefore likely to be reflected in CSF. Both ß-amyloid and tau proteins can reliably be measured in CSF and serve as biomarkers for AD.
This research project will contribute to the standardization of detailed standardized operating procedures for clinical use of CSF biomarkers for AD. To achieve this goal, two clinical algorithms for interpretation and reporting CSF biomarker values for AD diagnosis to referring clinicians will be tested and compared with regard to their diagnostic accuracy to discriminate (both clinically diagnosed and autopsy-confirmed) AD from controls and AD from non-AD dementia patients. Moreover, the influence of co-pathology in the brain on the diagnostic accuracy of both clinical algorithms will be studied. Emphasis will be put on cerebrovascular disease in definite AD patients and AD co-pathology in definite dementia with Lewy bodies (DLB) patients. Last but not least, the diagnostic accuracy of both clinical algorithms for diagnosing AD in its predementia disease stage will be tested through the comparison of progressive and stable mild cognitive impairment(MCI) patients. The two recently published sets of diagnostic criteria for ''prodromal AD'' (Dubois et al., 2010) and for ''MCI due to AD'' (Albert et al., 2011) will be compared with regard to their diagnostic performance. | | Duration | 01/01/2013 - 31/12/2014 | | Researcher(s) | | | Research Team(s) | |
- Research in the field of neurochemistry. 01/10/2012 - 30/09/2013
| Abstract | This project represents a formal research agreement between UA and on the other Inst. Born Bunge. UA provides Inst. Born Bunge research results mentioned in the title of the project under the conditions as stipulated in this contract. | | Duration | 01/10/2012 - 30/09/2013 | | Researcher(s) | | | Research Team(s) | |
- Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD). 01/06/2012 - 31/05/2015
| Abstract | Neurodegenerative disorders, represented mostly by Alzheimer''s disease (AD) and Parkinson''s
disease (PD), are characterised by progressive neuronal impairment and death. In spite of the brain''s
known capacity for regeneration, lost neurons generally cannot be replaced. Therefore, drugs aimed
at inhibiting neurodegenerative processes are likely to be most effective if the treatment is initiated as
early as possible in the disease process. However, clinical manifestations in early disease stages are
often difficult to diagnose. This is where biomarkers, specifically reflecting the onset of pathology may
have a profound impact on diagnosis and detection of treatment effects in the near future. A triplet of
cerebrospinal fluid (CSF) biomarkers for AD, total and hyperphosphorylated tau that reflect AD-type
axonal degeneration, and the 42 amino acid isoform of amyloid that reflects senile plaque pathology,
has already been established for early detection of AD before the onset of dementia. With regards to
PD, the most promising biomarker is CSF -synuclein. However, large variations in all biomarker
measurements have been reported between studies, both between and within centres and
laboratories. Such variations may be caused by pre-analytical, analytical, or assay-related factors and
seriously jeopardize the introduction of biomarkers in clinical routine and trials around the world.
The aim of BIOMARKAPD is to standardise the assessment of established and new fluid
biomarkers for AD and PD. To this end we will:
• Create and validate detailed standardised operating procedures for sample collection,
storage, analytical procedures and clinical use of biomarkers for AD and PD.
• Create an assay qualification algorithm specifying technical characteristics that must be
fulfilled to employ the assay in AD and PD biomarker studies and in clinical routine and trials.
• Create a network of harmonised laboratories around Europe and also implement a
certification system for laboratories and technicians with yearly hands-on training events and
external quality control surveys four times per year.
• Define a workflow for how new biomarkers can be developed from proof-of concept studies
to established biomarkers with reference limits, cut-offs and controlled confounders.
• Build a biobank for validating new biomarker candidates.
• Establish certified reference materials for biomarker measurements.
This is by far the most ambitious AD and PD biomarker standardisation programme to date, covering
the whole of Europe, as well as one Canadian site. The harmonisation of biomarker-related
procedures across Europe will facilitate clinical trials and allow for general implementation of the newly
proposed diagnostic guidelines for AD and new diagnostic approaches for PD in clinical routine. | | Duration | 01/06/2012 - 31/05/2015 | | Researcher(s) | | | Research Team(s) | |
- An integrated approach towards understanding the pathogenesis of neurodegeneration (NEUROBRAINNET). 01/04/2012 - 31/03/2017
| Abstract | We aim to establish an integrated network to identify genes and proteins involved in neurodegenerative disorders, determine their biological functions, establish their role in the pathophysiological processes, identify modifiers of the function by genetic screens, The network meets the prerequisites for such a project: frontline research in functional genomics related to human health, creating synergies with and between research efforts, teaming up with clinical groups through translational research for providing novel avenues for diagnosis, prevention, treatment and providing training and mobility to improve the skills of our young researchers. | | Duration | 01/04/2012 - 31/03/2017 | | Researcher(s) | | | Research Team(s) | |
- Biological markers for dementia (BIODEM). 01/10/2011 - 30/09/2014
| Abstract | Based on the CSF biomarkers β-amyloid1-42 protein (Aβ1-42), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau181P), diagnostic models for (differential) dementia diagnosis have been developed. Following determination of the added diagnostic value, these models will be validated for (early) dementia diagnosis. In order to improve discrimination between Alzheimer''s disease (AD) and non-AD dementias, new CSF markers will be investigated: Aβ1-40, TDP-43, α-synuclein. Moreover, this project will explore whether advanced neuroimaging measures and in vivo molecular neuro-imaging using β-amyloid- and tau-specific PET probes can be applied as biological markers for (early and differential) dementia diagnosis. Unravelling the role of various neurochemical markers in the pathophysiology of dementia (symptoms) might lead to the identification of new potential diagnostic markers and of new potential targets for (pharmacological) interventions. | | Duration | 01/10/2011 - 30/09/2014 | | Researcher(s) | | | Research Team(s) | |
- Pathophysiological mechanisms in amyloidosis mouse models. 01/10/2011 - 30/09/2014
| Abstract | Alzheimer''s disease (AD) is the most frequent form of neurodegenerative disease resulting in progressive loss of memory and cognitive abilities. AD is vastly becoming a major medical and social-economical problem in our ageing society. In Europe alone, approximately 7 million people suffer from AD. Despite intense research, pathophysiological mechanisms underlying AD and related disorders are still insufficiently documented. Valid animal models are essential in research ensuing elucidation of human
disease processes and testing of potential therapeutic strategies. The valid APP23 transgenic mouse model will be used to further study underlying pathophysiological mechanisms related to soluble aggregates of the amyloid-beta peptide and reactivation of the cell cycle in neurons, with presumed effects at the neurochemical, electrophysiological, morphological and behavioural level. In addition, a model for vascular dementia will be developed by crossing APP23 mice with atherogenic ApoE knockout mice.
Based on parallel genetic and environmental risk factors, pathophysiological aspects, and response to therapeutic interventions, it is assumed that convergent disease processes are the basis of AD and atherosclerosis. Behavioural, biochemical and pathological assessments will shed more light onto the link between AD and atherosclerosis, as well as the role of the amyloid precursor protein in atherosclerosis. | | Duration | 01/10/2011 - 30/09/2014 | | Researcher(s) | | | Research Team(s) | |
- Models of cerebellar disease: preclinical and clinical. 01/10/2011 - 30/09/2013
| Abstract | This project represents a formal research agreement between UA and on the other Neurosearch. UA provides Neurosearch research results mentioned in the title of the project under the conditions as stipulated in this contract. | | Duration | 01/10/2011 - 30/09/2013 | | Researcher(s) | | | Research Team(s) | |
- Biobanking and mib dementia of Alzheimer's and glaucoma. 15/09/2011 - 14/09/2013
| Abstract | This project represents a formal research agreement between UA and on the other hand MRFA. UA provides MRFA research results mentioned in the title of the project under the conditions as stipulated in this contract. | | Duration | 15/09/2011 - 14/09/2013 | | Researcher(s) | | | Research Team(s) | |
- Biomarkers for differential dementia diagnosis. 01/01/2011 - 31/12/2012
| Abstract | The CSF biomarkers Ab1-42, T-tau and P-tau181P have been developed to allow (early) dementia diagnosis. The contribution of biomarkers to the differential diagnosis between Alzheimer''s disease (AD) and non-AD dementias is clinically very relevant but remains poorly studied. The primary aim of the research project that is described in this grant application is to validate the role of the above-mentioned CSF biomarkers for differential AD versus non-AD dementia diagnosis using biomarker-based diagnostic models that have been developed in a population of autopsy-confirmed dementia patients. To achieve this goal, a large, independent population (n=1000) of patients with several forms of dementia will be included. Part of the population (n=200) will have autopsy-confirmed dementia diagnoses. Mainly the biomarker-based diagnostic model that allows discriminating AD from non-AD dementias will be tested.
The diagnostic potential of CSF Aβ1-40 for (differential) dementia diagnosis remains to be established. First, the diagnostic accuracy of CSF Aβ1-40 levels will be determined in a population of autopsy-confirmed dementia patients (n=200) and healthy control subjects (n=200). Second, the added diagnostic value of Aβ1-40 will be determined in two groups of equally large AD (n = 200) and non-AD (n = 200) patients that have as well been analyzed by the AD versus non-AD diagnostic biomarker-based model that is based on CSF Ab1-42, T-tau and P-tau181P levels (cfr. supra).
Last but not least, this research project will focus on differentiating dementia with Lewy bodies (DLB) and AD. Besides the typical Lewy bodies, the neuropathology of patients with DLB is also characterized by AD neuropathology. As a consequence, CSF biomarker profiles of DLB patients often is intermediate between AD and cognitively normal elderly, potentially hampering the application of CSF biomarkers for AD-DLB differential diagnosis. We therefore will study differences in CSF biomarker concentrations between neuropathologically confirmed DLB patients with and without AD lesions (senile plaques and neurofibrillary tangles according to the Braak stages) as compared to definite AD patients. | | Duration | 01/01/2011 - 31/12/2012 | | Researcher(s) | | | Research Team(s) | |
- Multiple Sclerosis, a multidisciplinary approach. 01/01/2010 - 31/12/2014
| Abstract | This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel. | | Duration | 01/01/2010 - 31/12/2014 | | Researcher(s) | | | Research Team(s) | |
- Characterisation of new targets for the treatment of the fragile X syndrome. 01/01/2010 - 31/12/2011
| Abstract | This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract. | | Duration | 01/01/2010 - 31/12/2011 | | Researcher(s) | | | Research Team(s) | |
- BOF: 1 year doctoral fellowship. 01/01/2010 - 31/12/2010
| Abstract | No abstract found | | Duration | 01/01/2010 - 31/12/2010 | | Researcher(s) | | | Research Team(s) | |
- Characterization and validation of biological markers of dementia and mild cognitive impairment 01/10/2009 - 30/09/2011
| Abstract | Mild cognitive impairment (MCI) is a clinical heterogeneous syndrome that is characterised by memory problems or other cognitive complaints that are not severe enough to fulfil the diagnostic criteria of dementia. The diagnosis of MCI refers to a state intermediate between normal ageing and dementia. Yearly, approximately 12% of the MCI patients convert to dementia, mostly AD, although a number of MCI patients remain stable or even improve and do not convert to dementia at all. Development of biological markers as an early diagnostic tool for the diagnosis of dementia (in particular Alzheimer''s disease) is of increasing importance given the future availability of disease-modifying drugs. This research project aims at the identification of genetic (APOE) and biological markers (proteins such as ß-amyloïd, tau and phospho-tau in easily accessible body fluids like cerebrospinal fluid and blood plasma) with a predictive value for conversion to dementia in MCI patients. Furthermore, the discriminatory power of these biomarkers for the differential diagnosis of dementia will be investigated. Patients will undergo thorough behavioural, genetic, neurochemical and neuropathological testing, providing us with a well-characterized study population. | | Duration | 01/10/2009 - 30/09/2011 | | Researcher(s) | | | Research Team(s) | |
- Neurochemical characterization of behavioral disturbances in dementia. 01/10/2009 - 30/09/2010
| Abstract | Behavioral disturbances (Behavioral and psychological signs and symptoms of dementia, BPSD) are an indispensable part of dementia and consist of delusions, hallucinations, aggressiveness, activity disturbances, diurnal rhythm disturbances, affective disorders and anxieties/phobias. Research has repeatedly confirmed that there is a neurochemical basis underlying BPSD although the pathophysiology remains unclear. In this project ante-mortem behavioral data will be correlated with neurotransmitter concentrations from regional dissection of post-mortem brain tissue of patients with various forms of dementia. Changes in different neurotransmitter systems will be mutually compared between different diagnostic categories of dementia in order to unravel possible neurochemical changes that predispose to certain behavioral profiles. | | Duration | 01/10/2009 - 30/09/2010 | | Researcher(s) | | | Research Team(s) | |
- Assessing the link between Alzheimer's disease and atherosclerosis in the APP23 x ApoE knockout mouse model. 01/02/2009 - 31/12/2010
| Abstract | Besides being pivotal Alzheimer''s disease proces, amyloid precursor protein is presumed to play a crucial rol in atherosclerosis as well. The link between both disorders will be studied in a cross model based on the APP23 transgenic amyloidosis Alzheimer''s model and the atherosclerosis-prone ApoE knockout model at the behavioural, biochemical, morphological and histopathological level. | | Duration | 01/02/2009 - 31/12/2010 | | Researcher(s) | | | Research Team(s) | |
- Pathophysiological mechanisms in amyloidosis mouse models for Alzheimer's disease. 01/01/2009 - 31/12/2012
| Abstract | This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel. | | Duration | 01/01/2009 - 31/12/2012 | | Researcher(s) | | | Research Team(s) | |
- Validation of biomarkers for dementia and mild cognitive impairment. 01/11/2008 - 31/10/2010
| Abstract | Diagnosis of sporadic Alzheimer''s disease (AD) is based on clinical exclusion criteria and the required diagnostic work-up is time-consuming and expensive at best resulting in a diagnosis of probable AD. In specialized centers, a diagnostic accuracy of maximally 68% is obtained. Besides, diagnosis is only definite on post-mortem neuropathological examination of the brain. Therefore, validated biological markers allowing diagnosing AD at an early stage of the disease are highly desirable.
In AD, several proteins accumulate in the brain. As the cerebrospinal fluid (CSF) is in close contact with the brain, those proteins can be detected in the CSF. Using biomarker-based models, a combined assessment of CSF levels of β-amyloid peptide (Aβ1-42), total tau protein (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) increases discriminatory power allowing differentiating AD from other dementias. As this combined assessment using newly developed biomarker-based models has not been validated and as its discriminatory power and its added diagnostic value remain to be established, we set up a prospective study, including dementia (n=800) and MCI (n=200) patients as well as healthy control subjects (n=200). As Aβ isoforms can be detected in plasma, diagnostic accuracy for (early) AD diagnosis will be tested as well. | | Duration | 01/11/2008 - 31/10/2010 | | Researcher(s) | | | Research Team(s) | |
- Characterisation and validation of biological markers of dementia and mild cognitive impairment. 01/01/2008 - 31/12/2010
| Abstract | As the biomarkers that have been selected for this research project are reflecting the neuropathology of several neurodegenerative dementias, we hypothesize that specific biomarkerprofiles will result in high levels of diagnostic accuracy, even in preclinical dementia stages. Following validation, new biomarker-based diagnostic models will be tested and apllied in a clinical-diagnostic setting. This research project will -last but not least- result in a better characterization of patients with mild cognitive impairment and several neurodegenerative dementias. | | Duration | 01/01/2008 - 31/12/2010 | | Researcher(s) | | | Research Team(s) | |
- Characterisation of new targets for the treatment of the fragile X syndrome. 01/01/2008 - 31/12/2009
| Abstract | No abstract found | | Duration | 01/01/2008 - 31/12/2009 | | Researcher(s) | | | Research Team(s) | |
- Identification of clinical characteristics and biomarkers with a predictive value for conversion to dementia in patients with mild cognitive impairment. 01/01/2008 - 31/12/2009
| Abstract | Mild cognitive impairment (MCI) is a heterogeneous clinically syndrome. Patients suffering from MCI have an increased risk to develop dementia. The aim of this research project is the identification of clinical characteristics (behavioural profiles) and biomarkers (APOE genotype and ¿-amyloïd1-42, total tau and tau phosphorylated at serine 181 in cerebrospinal fluid) with a predictive value for conversion to dementia in MCI patients. | | Duration | 01/01/2008 - 31/12/2009 | | Researcher(s) | | | Research Team(s) | |
- Biochemical, electrophysiological and ultrastructural analysis of neurotoxic APP cleavage products in transgenic mouse models for amyloidosis. 01/10/2007 - 30/09/2011
| Abstract | This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel. | | Duration | 01/10/2007 - 30/09/2011 | | Researcher(s) | | | Research Team(s) | |
- Characterization and validation of biological markers of dementia and mild cognitive impairment. 01/10/2007 - 30/09/2009
| Abstract | Mild cognitive impairment (MCI) is a clinical heterogeneous syndrome that is characterised by memory problems or other cognitive complaints that are not severe enough to fulfil the diagnostic criteria of dementia. The diagnosis of MCI refers to a state intermediate between normal ageing and dementia. Yearly, approximately 12% of the MCI patients convert to dementia, mostly AD, although a number of MCI patients remain stable or even improve and do not convert to dementia at all. Development of biological markers as an early diagnostic tool for the diagnosis of dementia (in particular Alzheimer''s disease) is of increasing importance given the future availability of disease-modifying drugs. This research project aims at the identification of genetic (APOE) and biological markers (proteins such as ß-amyloïd, tau and phospho-tau in easily accessible body fluids like cerebrospinal fluid and blood plasma) with a predictive value for conversion to dementia in MCI patients. Furthermore, the discriminatory power of these biomarkers for the differential diagnosis of dementia will be investigated. Patients will undergo thorough behavioural, genetic, neurochemical and neuropathological testing, providing us with a well-characterized study population. | | Duration | 01/10/2007 - 30/09/2009 | | Researcher(s) | | | Research Team(s) | |
- Biobank (Antwerp) of the Born Bunge Institute: supporting core facilities. 01/05/2007 - 31/12/2012
| Abstract | The primary research projects of the different laboratories of the IBB study Alzheimer''s disease and related conditions, Parkinson''s disease, frontotemporal dementias, Creutzfeld-Jacob disease, epilepsy, peripheral neuropathies and muscle disorders. The IBB focuses at a better integration and correlation of fundamental, clinical and neuropathological data concerning neurological conditions employing molecular genetics, biochemistry, experimental analyses of behavioural alterations and computational neurosciences. The IBB Biobank is a mutual initiative of the research units of the IBB department Neurology that is based upon the original brain bank. | | Duration | 01/05/2007 - 31/12/2012 | | Researcher(s) | | | Research Team(s) | |
- An integrated approach to the unraveling of the pathogenesis of CNS and PNS neurodegenerative disorders. 01/01/2007 - 31/12/2011
| Abstract | This project is designed to apply the unique information provided by sequencing of the human genome to further the understanding of and to develop treatments for these devastating diseases. The association in the proposed network of research groups in clinical research, human genetics and genomics, cell biology, proteomics, bioinformatics, and model organisms (mice, zebrafish and Drosophila), will create an integrated network to identify disease genes, determine their biological functions, establish their role in the pathophysiological processes and identify novel avenues for early diagnosis, treatment and prevention. | | Duration | 01/01/2007 - 31/12/2011 | | Researcher(s) | | | Research Team(s) | |
- Histopathological validation and characterisation of biological markers of dementia. 01/01/2007 - 31/12/2010
| Abstract | This research project aims at a histopathological validation and a better characterisation of neurchemical markers of dementia. This will lead to improved insights in biomarkers of dementia and their relation to the pathophysiology of dementia. The study design allows us to perform neuropathological and neurochemical analyses in different neurotransmitter nuclei of the CNS, moreover, the different neurochemical substances are analysed in CSF as well. | | Duration | 01/01/2007 - 31/12/2010 | | Researcher(s) | | | Research Team(s) | |
- Is the GABA (A) receptor a therapeutic target for treatment of the fragile X syndrome? 01/01/2007 - 31/12/2008
| Abstract | The fragile X syndrome is the most frequent form of hereditary mental retardation. Recently, our group found consistent underexpression of the delta subunit of the gamma-aminobutyric acid receptor type A in brains of fragile X knock out mice, a validated animal model for the fragile X syndrome. GABAA receptors are the principal inhibitory receptors of the brain and are involved in anxiety, depression, epilepsy, insomnia and learning and memory, processes disturbed in fragile X patients. This project attempts to increase our insights in the role of the GABAA receptor in the fragile X syndrome using a variety of molecular techniques. Furthermore we want to investigate whether the GABAA receptor is an appropriate target for treatment of this syndrome. A number of drugs specific for the GABAA receptor are already available on the market. | | Duration | 01/01/2007 - 31/12/2008 | | Researcher(s) | | | Research Team(s) | |
- Analysis of dendritic morphology in the APP23 model for Alzheimer's disease. 01/12/2006 - 31/12/2008
| Abstract | A longitudinal, morphometric study of dendrite morphology in the APP23 mouse model for Alzheimer''s disease will potentially reveal early stage, and presumably subtle forms of neuronal damage and neurodegeneration. Results will be correlated with age-dependent cognitive decline and amyloid pathology as previously published by our group. | | Duration | 01/12/2006 - 31/12/2008 | | Researcher(s) | | | Research Team(s) | |
- Prize "Robert Oppenheimer " 2004. 01/12/2006 - 31/12/2008
| Abstract | This scientific prize was given for my general scientific activities. | | Duration | 01/12/2006 - 31/12/2008 | | Researcher(s) | | | Research Team(s) | |
- Pathophysiological mechanisms in amyloidosis mouse models. 01/11/2006 - 31/10/2008
| Abstract | Up to date, no animal model mimics the complete range of histopathological, pathophysiological, cognitive and behavioural alterations, and all models, consequently, are partial models of AD. This research project, therefore, aims at detailed parallel analysis of several pathophysiological AD-related hypotheses in a selection of transgenic mouse models for amyloidosis and tau-related pathology. This approach will lead to reliable and sufficiently substantiated observations and we anticipate in bringing more clarity into the discussion between "baptists" and "tauists". | | Duration | 01/11/2006 - 31/10/2008 | | Researcher(s) | | | Research Team(s) | |
- The predictive value of biochemical parameters among which amino acids and amino acid analogues in the prognosis of an acute ischemic cerebrovascular accident. 01/10/2006 - 30/09/2008
| Abstract | No abstract found | | Duration | 01/10/2006 - 30/09/2008 | | Researcher(s) | | | Research Team(s) | |
- Characterisation of neurochemical markers of dementia. 01/07/2006 - 31/12/2010
| Abstract | This project aims to characterise neurochemical markers of dementia across diagnostic categories (n = 500). The different neurotransmitter systems (noradrenergic, adrenergic, serotonergic, dopaminergic and cholinergic systems) will undergo an in-depth neurochemical, genetical and histopathological characterisation and will be correlated with phenotypical (cognitive and behavioural) characteristics of the study population. | | Duration | 01/07/2006 - 31/12/2010 | | Researcher(s) | | | Research Team(s) | |
- Functional peptidomics. 01/03/2006 - 28/02/2010
| Abstract | Novel candidate bioactive peptides will be extracted from selected mouse tissues and identified by a combination of liquid chromatography and advanced mass spectrometry. We will try to assign a function to the peptides via a systematic series of analysis steps, supported by advanced data mining on a comprehensive peptide database that will include relevant public domain information as well as all project results. Thus peptides will be prioritized dynamically for experimental testing based on the best evidence available.
Bioinformatics analysis will look for known hallmarks of bioactive peptides (precursor with signal peptide, flanking motifs for cleavage, sequence conservation across species, etc.) as well as newly derived properties. Such novel features may be derived from relational data mining. The bioinformatics and relational data mining tools will be developed for the peptidomics data but in such a way that they can be applied more generally to other ¿omics projects, i.e. research programmes that can be phrased in terms of a set of relevant genes.
Promising peptides will be synthesized and tested on a panel of approximately 60 cell lines representative of major cell types using a method such as microphysiometry that can detect cellular activation independent of the type of activated signal transduction cascade. Because the gut is (together with the brain) the richest source of bioactive peptides, all novel peptides will also be tested in organ assays of various segments of the gastro-intestinal tract. Peptide expression will be mapped by in situ hybridization of the precursor mRNA.
Peptides of sufficient interest will be radio-labeled for binding studies on tissue sections and for pharmacokinetic studies (including whole animal PET and SPECT). The pharmacokinetic studies will reveal the time-course of the peptide concentration in various compartments of interest (blood, CNS) as well as the organs where a peptide preferentially localizes. Competition with unlabeled competitors will help to distinguish whether such localization is due to the peptide binding to a specific receptor or being concentrated e.g., in an excretory system.
If sufficient indications for a CNS action are found (mENA expression, peptide binding on brain sections, penetration of blood brain barrier, etc.), behavioural studies will be initiated. These again will use a multi- tiered strategy, starting with simple tests covering a variety of behavioural functions and gradually zooming in on specific functions with more specialized tests. | | Duration | 01/03/2006 - 28/02/2010 | | Researcher(s) | | | Research Team(s) | |
- Evaluation of APP-related molecules in the APP23 transgenic mouse model for Alzheimer's disease. 01/03/2006 - 31/12/2007
| Abstract | The link between amyloid ß pathology and clinical symptomatology in Alzheimer''s disease is insufficiently convincing. Recently, the amyloid cascade theory was complemented with non-fibrillary soluble Aß oligomeres (Aß-derived diffusible ligands (ADDL), which could form the missing link in the disease process. ADDL and other amyloid precursor protein related molecules will be analyzed in the extensively validated APP23 transgenic mouse model. | | Duration | 01/03/2006 - 31/12/2007 | | Researcher(s) | | | Research Team(s) | |
- Identification and characterisation of neurochemical markers for dementia. 01/01/2006 - 31/12/2006
| Abstract | No abstract found | | Duration | 01/01/2006 - 31/12/2006 | | Researcher(s) | | | Research Team(s) | |
- Clinical and behavioural correlates of biological markers of dementia and mild cognitive impairment. 01/12/2005 - 31/12/2005
| Abstract | No abstract found | | Duration | 01/12/2005 - 31/12/2005 | | Researcher(s) | | | Research Team(s) | |
- Characterization of biological markers of dementia. 01/11/2005 - 31/10/2007
| Abstract | Diagnosis of sporadic Alzheimer''s disease (AD) is based on clinical exclusion criteria and the required diagnostic work-up is time-consuming and expensive at best resulting in a diagnosis of probable AD. In specialized centers, a diagnostic accuracy of maximally 65-90 % is obtained. Besides, diagnosis is only definite on post-mortem neuropathological examination of the brain. Therefore, a validated biological marker allowing diagnosing AD at an early stage of the disease is highly desirable.
In AD, several proteins accumulate in the brain. As the cerebrospinal fluid (CSF) is in close contact with the brain, those proteins can be detected in the CSF. CSF levels of beta-amyloid protein (BAP) are decreased in AD patients compared to age-matched controls whereas CSF levels of protein tau (tau), hyperphosphorylated tau (P-tau) are increased compared to controls. The determination of BAP, tau or P-tau helps discriminating AD from normal aging or depression. However, as changes in biomarker levels are found in other dementia syndromes too, the discriminatory power of each biomarker separately is too small to allow differentiation between AD and other forms of dementia. We hypothesize that a combined assessment of CSF levels of BAP, tau and P-tau increases discriminatory power allowing differentiating AD from other dementias or to identify patients with incipient AD. As this combined assessment has not been validated and as its discriminatory power and its added diagnostic value remain to be established, we set up a prospective study.
Aims:
(1) To validate and to establish the added value of a combined assessment of CSF levels of BAP, tau and P-tau for diagnosing AD and for discriminating AD from other forms of dementia.
(2) To establish the predictive value of a combined assessment of CSF levels of BAP, tau and P-tau for the conversion to AD in patients with mild cognitive impairment (patients with isolated memory problems, not severe enough to allow diagnosing a dementia; many of those patients appear to have incipient AD).
(3) The identification of specific clinical, behavioral and neuropsychological symptoms that are associated with certain biomarker profiles. | | Duration | 01/11/2005 - 31/10/2007 | | Researcher(s) | | | Research Team(s) | |
- Characterisation and validation of biological markers of dementia and mild cognitive impairment. 01/10/2005 - 30/09/2008
| Abstract | This research project wil! establish the role and value of BAP, tau, P-tau and APOE as biomarkers in the diagnostic work up of MCI and dementia in a large population of patients of which a substantial number wil! get neuropathological confirmation of clinical diagnosis of dementia. The research project wil! moreover lead to a better characterisation of the several disease groups studied and wil! probably identify subgroups of patients with common biochemica! and/or behavioural features. | | Duration | 01/10/2005 - 30/09/2008 | | Researcher(s) | | | Research Team(s) | |
- Molecular biological, pharmacological, neurochemical and behavioral genotyping of mice for dementia. 01/10/2005 - 30/09/2007
| Abstract | No abstract found | | Duration | 01/10/2005 - 30/09/2007 | | Researcher(s) | | | Research Team(s) | |
- Pathophysiological mechanisms and neurochemical en electrophysiological alterations in transgenic mouse models for amyloidosis. 01/10/2005 - 30/09/2006
| Abstract | No abstract found | | Duration | 01/10/2005 - 30/09/2006 | | Researcher(s) | | | Research Team(s) | |
- Predictive value of guanidino compounds in the acute phase of an ischemic cerebrovascular accident. 01/10/2005 - 30/09/2006
| Abstract | No abstract found | | Duration | 01/10/2005 - 30/09/2006 | | Researcher(s) | | | Research Team(s) | |
- Characterisation and validation of biological markers of dementia and mild cognitive impairment. 01/05/2005 - 31/12/2006
| Abstract | This research project aims to establish (1) the added diagnostic value of a combined analysis of b-amyloid protein(1-42), protein tau and Phospho-tau in CSF (with/without APOE genotyping) to discriminate Alzheimer''s disease from other forms of dementia in 500 clinically diagnosed and 100 neuropathologically confirmed dementia subjects; (2) the predictive value of such a combined biomarker analysis for the conversion to dementia in 150 subjects with mild cognitive impairment. | | Duration | 01/05/2005 - 31/12/2006 | | Researcher(s) | | | Research Team(s) | |
- Support maintenance scientific equipment. 01/01/2005 - 31/12/2013
| Abstract | No abstract found | | Duration | 01/01/2005 - 31/12/2013 | | Researcher(s) | | | Research Team(s) | |
- Behavioural phenotyping of transgenic mouse models for human disorders with cognitive deficits : aetiological research and innovating therapies. 01/01/2005 - 31/12/2008
| Abstract | In the research project, different transgenic mouse lines will be studied. Behavioural phenotyping will be accomplished in collaboration with (inter)national research groups that have the indispensable experience and willingness for the construction and genotypic support of transgenic mouse lines. | | Duration | 01/01/2005 - 31/12/2008 | | Researcher(s) | | | Research Team(s) | |
- Is the GABA (A) receptor a therapeutic target for treatment of the fragile X syndrome? 01/01/2005 - 31/12/2006
| Abstract | The fragile X syndrome is the most frequent form of hereditary mental retardation. Recently, our group found consistent underexpression of the delta subunit of the gamma-aminobutyric acid receptor type A in brains of fragile X knock out mice, a validated animal model for the fragile X syndrome. GABAA receptors are the principal inhibitory receptors of the brain and are involved in anxiety, depression, epilepsy, insomnia and learning and memory, processes disturbed in fragile X patients. This project attempts to increase our insights in the role of the GABAA receptor in the fragile X syndrome using a variety of molecular techniques. Furthermore we want to investigate whether the GABAA receptor is an appropriate target for treatment of this syndrome. A number of drugs specific for the GABAA receptor are already available on the market. | | Duration | 01/01/2005 - 31/12/2006 | | Researcher(s) | | | Research Team(s) | |
- Clinical and animal-experimental research of the neurochemical and behavioural aspects of 'Behavioural and Psychological Signs and Symptoms of Dementia" (BPSD). 01/10/2004 - 30/09/2006
| Abstract | No abstract found | | Duration | 01/10/2004 - 30/09/2006 | | Researcher(s) | | | Research Team(s) | |
- No title found 01/10/2004 - 31/12/2004
| Abstract | No abstract found | | Duration | 01/10/2004 - 31/12/2004 | | Researcher(s) | | | Research Team(s) | |
- Support of neurological and cardiovascular scientific investigation conducted by the UA by/or in association with Born-Bunge Foundation. 01/01/2004 - 31/12/2007
| Abstract | No abstract found | | Duration | 01/01/2004 - 31/12/2007 | | Researcher(s) | | | Research Team(s) | |
- Clinical and behavioural correlates of biological markers of dementia and mild cognitive impairment. 01/12/2003 - 30/11/2005
| Abstract | No abstract found | | Duration | 01/12/2003 - 30/11/2005 | | Researcher(s) | | | Research Team(s) | |
- Design and validation of a neurophysiological test of cognition in multiple sclerose. 01/10/2003 - 30/09/2006
| Abstract | No abstract found | | Duration | 01/10/2003 - 30/09/2006 | | Researcher(s) | | | Research Team(s) | |
- Neurochemical correlates of behavioral and psychological signs and symptoms of Dementia of the Alzheimer Typen and Frontal Lobe Dementia. 01/10/2003 - 30/09/2004
| Abstract | The aim of the present study is to trace for neurochemical correlates of BPSD in a population of DAT and FLD patients. We will focus on paranoid and delusional ideations, hallucinations, aggressiveness, affective distrubances and anxiety. Rating scales for BPSD will be used for reasons of standardization and quantification of observations. Especially serotonergic and catecholaminergic neurotransmitter systems will be studied as a physiopathological link with psychosis, aggressive behavior, depression and anxiety is presumed.
As amino acid neurotransmitters have not systematically been studied in these patients related tot BPSD, we will trace for possible correlations in this field as well. Patients will be compared with age-matched controls in order to determine the disease specificity of the correlations revealed. | | Duration | 01/10/2003 - 30/09/2004 | | Researcher(s) | | | Research Team(s) | |
- Phosphomannomutases in human and mouse : characterization of a novel gene family and establisment of a mouse model for Carbohydrate-Deficient-Glycoprotein Syndrome Type I (CDG1) 01/10/2003 - 31/12/2003
| Abstract | Congenital disorders of glycosylation constitute a group of inborn errors of metabolism characterized by defects in N-glycosylation of cellular and serum proteins. Different types of such disorders have been described, however, the phosphomanomutase deficiency, CDG-Ia, remains the most frequent form. The human disorder CDG-Ia, which causes severe deficits of the central nervous system and other organ systems, appeared to be due to mutations in the PMM2 gene. The purposes of the present project are the study of the expression and characteristics of the PMMs, as well as the construction of transgenic murine models to examine the fuctions of the PMMs. The recently available PMM1 knockout mice have been tested in a battery of behavioral tests, and appeared to be indistinguishable from controls on all of the neurobehavioural functions tested. Construction of a PMM2 knockout is one of the main purposes of the present project, and the model will also be tested on different functions. In the behavioural study of these models, tests of different aspect of mouse behaviour will be used (locomotor activity, exploration, motor coordination, emotional responses, different forms of learning and conditioning, etc.). | | Duration | 01/10/2003 - 31/12/2003 | | Researcher(s) | | | Research Team(s) | |
- Evaluation of uremic retention solutes as candidate neurotoxines. 01/10/2003 - 31/12/2003
| Abstract | This project is characterized by a multidisciplinary approach to the study of uremic neurotoxines. In a first phase we will attempt to identify the accumulated substances by fractionation of a variety of biological fluids of renal insufficient individuals. The different fractions will consequently be tested in different in vitro and in-vivo settings (respectively on neurones in culture and in experimental animals after ICV or more localized application. Effects on neurotransmission, excitotoxicity and behavioral manifestations (e.g. epilepsy and cognition) will be investigated. In a second phase, we will study the protein binding of the identified uremic neurotoxins and will thereafter attempt to optimize the dialysability of the identified substances. | | Duration | 01/10/2003 - 31/12/2003 | | Researcher(s) | | | Research Team(s) | |
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Expertise
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Show the team expertise- De Deyn Peter
- Behavioural phenotyping of mouse models and preclinical evaluation of symptomatic and preventive therapeutic interventions in validated transgenic mouse models for Alzheimer's disease.
| Technique: | Neuromotor abilities: accelerating Jones-Roberts rotarod for mice, Dunham-Miya rotarod for rats and mice, wire suspension test, gait test, stationary beam task, wire suspension test;
Activity and exploration: open field activity and exploration (incl. social) with computerized video-tracking, dark-light transition box with digital counter, computerized registration of cage activity patterns;
Learning tests: step-through box and small animal shocker for active and passive avoidance training, plus-shaped water maze, Morris water maze with computerized video-tracking for hidden and visible escape training, automated operant conditioning chambers with data acquisition software for reward and punishment conditioning protocols, manual conditioning chamber for contextual fear conditioning;
Analysis of behavioural alterations (anxiety, depression, etc.): forced swim test, tail suspension test, sucrose preference task, holeboard, elevated plusmaze
Apparatus for electrographic and evoked potential recording in rats and mice; Neural cell culture room and equipment | | Users: | - Clinical neuroscientists
- Molecular biologists (a.o. geneticists)
- Farmaceutical industry
- Metabolic-diagnostic departments | | Keywords: | BEHAVIOURAL NEUROSCIENCE, BIOGENIC AMINES ANALYSIS, HPLC, AMINO ACID ANALYSIS, BIOMARKER |
- Metabolic and neurochemical analyses.
| Technique: | Amino acid and amino acid analogue analysers using cation exchange resin, HPLC-apparatus: A BAS 200B chromatograph (BAS, West Lafayette, USA) and a BIO-TEK HPLC system (Beun-De Ronde Serlabo, Drogenbos, Belgium) are used for analyses of a.o. biogenic amines. Microdialysis equipment for in vivo and ex vivo neurochemical analysis in rodents is available, as well as ample experience with ELISA techniques. | | Users: | - Clinical neuroscientists
- Molecular biologists (a.o. geneticists)
- Farmaceutical industry
- Metabolic-diagnostic departments | | Keywords: | BEHAVIOURAL NEUROSCIENCE, BIOGENIC AMINES ANALYSIS, HPLC, AMINO ACID ANALYSIS, BIOMARKER |
- 1) Metabolic and neurochemical analyses
2) Behavioural phenotyping of mouse models and preclinical evaluation of symptomatic and preventive therapeutic interventions in validated transgenic mouse models for Alzheimer's disease
3) Diagnostic reference centre for biomarkers in dementia
4) Scientific consulting
5) Brain banking| Technique: | Apparatus for diagnostic and therapeutic procedures in neurological clinical practice
Neuroimaging apparatus: fMRI, MRS, (neuro-activation) SPECT; Pupil assay lab; Updated databases and available patient populations for virtually all fields of clinical neurology; Neurocognitive test instruments : Middelheim Frontality score (MFS) and Emotional Facial Recognition task (EFRT). | | Users: | - Clinical neuroscientists
- Molecular biologists (a.o. geneticists)
- Farmaceutical industry
- Metabolic-diagnostic departments | | Keywords: | BEHAVIOURAL NEUROSCIENCE, BIOGENIC AMINES ANALYSIS, HPLC, AMINO ACID ANALYSIS, BIOMARKER |
- Engelborghs Sebastiaan
- Marescau Bartold
- Amino acid analyses, guanidino compound analyses, orotic acid, creatinine and urea determinations.
| Technique: | - Amino acid analyses: cation exchange liquid chromatography, colorimetric and fluorescence determination.
- Guanidino compound analyse : idem, with fluorescence detection.
- Orotic acid, urea and creatinine determinations : spectrophotometry. | | Users: | - Clinical biologists
- Researchers in biological and in biomedical sciences
- Pharmaceutical and food industry | | Keywords: | NITROGEN METABOLISM, PROTEIN METABOLISM, PATHOPHYSIOLOGY, CREATININE, UREA, OROTIC ACID, AMINO ACIDS, GUANIDINO COMPOUNDS |
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