Biomarkers for differential dementia diagnosis.

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.

Keywords:DEMENTIA, NEUROCHEMISTRY, BIOLOGICAL MARKERS

Disciplines:Laboratory medicine, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing