Comparison of plasma soluble and extracellular vesicles-associated biomarkers in Alzheimer's disease patients and cognitively normal individuals.

Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101511643 Publication Model: Electronic Cited Medium: Internet ISSN: 1758-9193 (Electronic) NLM ISO Abbreviation: Alzheimers Res Ther Subsets: MEDLINE

Original Publication: [London] : BioMed Central Ltd.

Alzheimer Disease*/blood ; Extracellular Vesicles*/metabolism ; Biomarkers*/blood ; Amyloid beta-Peptides*/blood ; tau Proteins*/blood; Humans ; Female ; Male ; Aged ; Peptide Fragments/blood ; Aged, 80 and over ; Middle Aged ; Cohort Studies ; Apolipoprotein E4/genetics ; Apolipoprotein E4/blood

Background: Amyloid-β (Aβ) and tau are brain hallmarks of Alzheimer's disease (AD), also present in blood as soluble biomarkers or encapsulated in extracellular vesicles (EVs). Our goal was to assess how soluble plasma biomarkers of AD pathology correlate with the number and content of EVs.
Methods: Single-molecule enzyme-linked assays were used to quantify Aβ42/40 and tau in plasma samples and neurally-derived EVs (NDEVs) from a cohort of APOE ε4- (n = 168) and APOE ε4+ (n = 68) cognitively normal individuals and AD patients (n = 55). The ratio of CD56 (Neuronal cell-adhesion molecule) to CD81 signal measured by ELISA-DELFIA was used for the relative quantification of NDEVs in plasma samples.
Results: The soluble plasma Aβ42/40 ratio is decreased in AD patients compared to cognitively normal individuals. The amount and content (Aβ40, Aβ42, tau) of plasma NDEVs were similar between groups. Plasma NDEVs quantity remain consistent with aging and between AD and CN individuals. However, the quantity of soluble biomarkers was negatively correlated to NDEVs number in cognitively normal individuals, while in AD patients, this correlation is lost, suggesting a shift in the mechanism underpinning the production and the release of these biomarkers in pathological conditions.
Conclusion: Soluble plasma Aβ42/40 ratio is the most robust biomarker to discriminate between AD patients and CN individuals, as it normalizes for the number of NDEVs. Analysis of NDEVs and their content pointed toward peculiar mechanisms of Aβ release in AD. Further research on independent cohorts can confirm our findings and assess whether plasma Aβ and tau need correction by NDEVs for better AD risk identification in CN populations.
(© 2024. The Author(s).)

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ARC21/26-114 UCLouvain Action de Recherche Concertée; ARC21/26-114 UCLouvain Action de Recherche Concertée; ASP40001844 Fonds De La Recherche Scientifique - FNRS; CCL40010417 Fonds De La Recherche Scientifique - FNRS; FNRS J.0106.22 Fonds De La Recherche Scientifique - FNRS; 40010035 Fonds de la Recherche Fondamentale Stratégique - Walloon Excellence in Life Sciences and Biotechnology; SAO-FRA 2020/0028 SAO-FRA Alzheimer's Research Foundation; SAO-FRA 2018/0025 SAO-FRA Alzheimer's Research Foundation

Keywords: Alzheimer’s disease; Aβ42/40 ratio; Blood biomarkers; Extracellular vesicles; Neurally-derived EVs; Tau

0 (Biomarkers)
0 (Amyloid beta-Peptides)
0 (tau Proteins)
0 (Peptide Fragments)
0 (amyloid beta-protein (1-42))
0 (Apolipoprotein E4)
0 (amyloid beta-protein (1-40))

Date Created: 20240629 Date Completed: 20240629 Latest Revision: 20240712

20240713

PMC11212434

10.1186/s13195-024-01508-6

38943196