Research Sebastiaan Engelborghs

Abstract

Ischemic stroke (IS) and Alzheimer's disease (AD) are both common neurological diseases. IS can be defined as the sudden onset of a focal neurological deficit due to loss of regional blood supply. AD manifests by core features of progressive memory impairment, visuospatial decline and loss of executive functions. Cognitive worsening in general and an increased rate of cognitive decline in AD patients after stroke has already been reported. In both AD and IS, neurogenesis seems to play an important role. After IS, aberrant neurogenesis seems to interfere with the existing hippocampal circuitry and can therefore influence cognitive functioning. We hypothesize that stroke-induced cognitive decline is more pronounced in AD mice than in WT controls as a result of aberrant neurogenesis. This hypothesis will be tested in an animal study using a well-established AD (3xTg) mouse model, a stroke mouse model by middle cerebral artery occlusion (MCAO) and a combined model. We will investigate the role of neurogenesis after stroke in AD mice and how their cognitive performance in memory tasks is influenced. To this purpose, temozolomide (TMZ, inhibitor of neurogenesis) and memantine (MEM, stimulator of neurogenesis) will be administered. We will assess the effect of both treatments on cognitive performance and various markers of AD progression, neurodegeneration, inflammation and neurogenesis. If successful, a future similar clinical investigation could be set up.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

• Experimental Neurobiology Unit (ENU)

Project type(s)

• Research Project

Abstract

Due to overlapping clinical and pathological features, the differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) becomes extremely difficult. Besides, there still is no approved treatment for DLB. The current application, therefore, aims at identifying neurochemical markers in blood (serum) and cerebrospinal fluid (CSF) to improve the diagnostic accuracy among these syndromes. Based on our previous data, DLB-specific alterations in the locus coeruleus, a small noradrenergic brainstem nucleus, may provide rationale to address these challenges. The same goes for the neuroinflammatory marker lipocalin-2 (LCN2), of which expression levels in the substantia nigra are increased. Overall, this proposal intends to (i) analyze various neurochemical compounds in serum/CSF as potential disease-specific biomarkers with a demonstrated link to underlying brain pathology. Here, our main focus will be on the noradrenergic neurotransmitter system (3-methoxy-4-hydroxyphenylglycol; noradrenaline) and LCN2. We will also study in detail (ii) if these marker alterations are associated with the clinical follow-up diagnosis and measured noradrenergic tracer uptake values after MIBG-scintigraphy. Finally, this study will (iii) meticulously process and analyze brain material, allowing us an in-depth evaluation of the regional distribution of alfa-synuclein and AD-related pathology, linked to the monoaminergic and neuroinflammatory markers previously determined.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Engelborghs Sebastiaan
• Fellow: Vermeiren Yannick

Research team(s)

• Experimental Neurobiology Unit (ENU)

Project type(s)

• Research Project

Abstract

Alzheimer's disease (AD) is the most frequent global cause of severe cognitive impairment. Epileptic seizures have always been thought to be a late complication in a minority of AD patients. We hypothesise that subclinical epileptic phenomena do however occur in a considerable part of AD patients much earlier in the disease course which aggravates cognitive decline. We will test this hypothesis in a prospective, longitudinal observational clinical study. Moreover, we will investigate the onset and frequency of epileptiform discharges in well-established transgenic AD mouse models and how their cognitive performance in memory tasks is influenced. Next we propose an early intervention with antiseizure drugs as a possible disease modifying therapy. To this end, AD mice will be chronically treated with a clinically used antiseizure drug levetiracetam or with a ghrelin receptor agonist in development. Levetiracetam was previously shown to exhibit antiepileptogenic properties, while ghrelin receptor agonism inhibits cognitive deficits in AD models and reduces seizures in epilepsy mouse models. We will assess the effect of both treatments on epileptiform biomarkers, cognitive performance and various markers indicative of AD progression. If successful, we could set up future clinical investigations with chronic treatment of levetiracetam in patients with mild cognitive impairment due to AD.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

• Experimental Neurobiology Unit (ENU)

Project type(s)

• Research Project

Abstract

Service agreement between Universiteit Antwerpen (UAntwerp), with registered offices at Prinsstraat 13, 2000 Antwerpen, and the Belgian Neurological Society vzw (BNS), with registered offices at University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (T6.57). The parties agree as follows: UAntwerp shall perform certain services namely 'administration of the BNS' BNS shall make available all necessary information to enable UAntwerp to properly perform the Services.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

Alzheimer's disease (AD) is the most frequent global cause of severe cognitive impairment. Epilepsy, characterised by repetitive unprovoked seizures, is more prevalent in AD patients than in healthy controls. We hypothesise that subclinical epileptic phenomena occur in a considerable part of AD patients which aggravates cognitive decline. We therefore propose an intervention with antiseizure drugs early in the disease course as a possible disease modifying therapy. We will test this hypothesis in well-established transgenic AD mouse models. First, we will investigate the onset and frequency of epileptiform discharges in AD mice and how cognitive performance in memory tasks is influenced. Next, AD mice will be chronically treated with a clinically used antiseizure drug levetiracetam or with a ghrelin receptor agonist in development. Ghrelin is an endogenous mediator, mainly involved in metabolism. Research has indicated that ghrelin inhibits cognitive deficits in AD and reduces seizures in epilepsy mouse models. We will assess the effect of both treatments on epileptiform biomarkers, cognitive performance and various markers indicative of AD progression.

Researcher(s)

• Promoter: Engelborghs Sebastiaan
• Co-promoter: Nagels Guy
• Fellow: Vande Vyver Maxime

Research team(s)

Project type(s)

• Research Project

Abstract

Neurodegenerative diseases represent a heavy and increasing burden for patients and their care-givers, and the health care system in general. Therefore, novel strategies for early diagnosis and effective treatments are needed to stop this societal time bomb. Most patients develop Alzheimer's disease late in life without strong genetic predispositions. The disease is assumed to be triggered by a combination of physiological factors, in particular ageing and environmental factors, such as pollutants, and lifestyle. The molecular and cellular mechanisms affected by these factors are not understood, and are the subject of the new project 'Herinneringen' ('Memories') (01.01.2018 - 31.12.2020). Mechanistic understanding will be acquired by applying differential genomics analysis on neuronal cell models derived from pluripotent stem cells generated from healthy individuals, individuals with mild cognitive impairment, and patients with various degrees of dementia, including Alzheimer's disease, following in-vitro exposure to toxins. This information will then be validated against biological samples from patients representing similar human cohorts. Advancing our understanding of the mechanisms underlying the earliest stages of dementia development will facilitate the creation of novel tools for early diagnosis. New opportunities for development of drugs addressing early events in disease progression are also expected to emerge from the project as well, and this combined with better methods for pre-clinical and clinical efficacy assessment of novel drugs. The new knowledge will also enable to generate improved animal models of Alzheimer's disease required for development of novel therapeutic strategies. Finally, the project may help to implement preventive measures to decrease the incidence of Alzheimer's disease, by for instance advocating life style changes or reducing emission of neurotoxic substances.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project website

Project type(s)

• Research Project

Abstract

This is a sequential, open-label, multicenter Phase 1 study and consisting of the following consecutive parts: Part A, in healthy adult male subjects; Part B, in mild AD subjects and healthy age- and gender-matched controls.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between the parties UAntwerpen and on the other hand, BNS. UAntwepren provides BNS research results under the conditions as stipulated in the present document.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

The past decade, a lot of progress has been made with regard to standardization and harmonization of existing biomarkers for AD. As the development of treatments for AD moves increasingly into the preclinical stage of the disease, biomarkers will take on an important role. The standardization and harmonization is essential as this will lead to the ability to reduce/control variability of measurement methodologies and to improve the observation of treatment effects. Eventually, the standardization and harmonization efforts can lead to study comparisons and ease the transition from research into clinical trials/clinical practice.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan
• Co-promoter: De Deyn Peter

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Stroobants Sigrid
• Co-promoter: Engelborghs Sebastiaan
• Co-promoter: Parizel Paul
• Co-promoter: Sijbers Jan

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia, after Alzheimer's disease (AD). Given that FTLD indeed mostly affects middle-aged individuals, this debilitating disease has a dramatic effect on the patients' personal as well as professional life. The differential diagnosis of dementia based on a clinical diagnosis and with the help of AD biomarkers in cerebrospinal fluid is still suboptimal. Unfortunately, well-characterized and validated diagnostic markers for FTLD do not yet exist. With the discovery of TAR DNA-binding protein of 43 kDa (TDP-43) as the major disease protein in 50-60% of this clinically and genetically heterogeneous group of FTLD patients, a potential diagnostic marker for FTLD-TDP was identified. The current project aims to (1) generate new TDP-43 antibodies and characterize TDP-43; (2) develop an immunoassay to quantify TDP-43 in biological samples and (3) assess its diagnostic potential, for which samples from confirmed FTLD-TDP and AD patients will be used. If successful, this project will provide new tools (well-characterized TDP-43 antibodies and an immunoassay) for researchers to unravel the TDP-43 pathogenesis, leading to new research hypotheses and possible therapeutic ventures. By applying the TDP-43 immunoassay as a tool to identify FTLD-TDP patients, we hope to improve (differential) dementia diagnostics as well as contribute to progress within the field of other TDP-pathologies.

Researcher(s)

• Promoter: Engelborghs Sebastiaan
• Co-promoter: van der Zee Julie
• Fellow: Goossens Joery

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

Abstract

The general objectives of this project are to develop a BACE inhibitor for disease modification in Alzheimer's disease and to explore the development in an earlier prodromal Alzheimer's disease population. From a drug development perspective, this will involve multiple adaptation steps and the intensive use of biomarkers.

Researcher(s)

• Promoter: Engelborghs Sebastiaan
• Co-promoter: Stroobants Sigrid

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Cras Patrick
• Co-promoter: Engelborghs Sebastiaan
• Co-promoter: Van Dam Debby

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan
• Fellow: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Engelborghs Sebastiaan
• Fellow: Le Bastard Nathalie

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Engelborghs Sebastiaan
• Fellow: Vermeiren Yannick

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Co-promoter: Engelborghs Sebastiaan
• Co-promoter: Marescau Bartold

Research team(s)

Project type(s)

• Research Project

Abstract

This scientific prize was given for my general scientific activities.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Fellow: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Fellow: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: De Deyn Peter
• Fellow: Engelborghs Sebastiaan

Research team(s)

Project type(s)

• Research Project