Amyloid-? peptides in cerebrospinal fluid of patients with dementia with Lewy bodies.

ABSTRACT:

Background

One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-? (A?) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) A? peptides (A?38, A?40, A?42) in DLB, Alzheimer's disease (AD), and cognitively normal controls.

Methods

CSF from patients with DLB (n =?72; age 68?±?6?years; 10%F; Mini-mental State examination (MMSE) 23?±?4), AD (n =?38; age 68?±?6?years; 8%F; MMSE 22?±?5), and cognitively normal controls (n =?38; age 67?±?7?years; 13%F; MMSE 29?±?2) was analyzed using the Meso Scale Discovery assay for human A? peptides. We performed general linear models to compare CSF A? peptide levels between groups. Associations between CSF A? peptides and MMSE score at baseline and longitudinal changes over time were assessed with linear mixed models.

Results

For all three CSF A? peptides and compared to controls (A?38 2676?±?703?pg/ml, A?40 6243?±?1500?pg/ml, and A?42 692?±?205?pg/ml), we observed lower levels in DLB (A?38 2247?±?638, A?40 5432?±?1340, and A?42 441?±?185, p ?0.52) and APOE genotype. Finally, lower A? peptide levels were associated with lower MMSE score (? =?1.02-1.11, p ConclusionWe demonstrated different profiles of CSF A? reduction in DLB and AD. In particular, while AD is characterized by an isolated drop in A?42, DLB comes with reductions in A?38, A?40, and A?42. This suggests that amyloid metabolism is affected in DLB, even in the absence of co-morbid AD pathology.

SUBMITTER: van Steenoven I 

PROVIDER: S-EPMC6788069 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature