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Project

Monoaminergic and neuroinflammatory markers in dementia with Lewy bodies to improve differential dementia diagnosis.

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.
Date:1 Nov 2019 →  31 Oct 2022
Keywords:BIOFLUIDS, ALZHEIMER'S DISEASE, BIOMARKERS
Disciplines:Analytical biochemistry, Neurological and neuromuscular diseases, Behavioural neuroscience, Pathophysiology, Biomarker discovery
Project type:Collaboration project