Comparison of plasma soluble and extracellular vesicles-associated biomarkers in Alzheimer's disease patients and cognitively normal individuals.
Alzheimer’s disease
Aβ42/40 ratio
Blood biomarkers
Extracellular vesicles
Neurally-derived EVs
Tau
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
28 Jun 2024
28 Jun 2024
Historique:
received:
15
04
2024
accepted:
19
06
2024
medline:
29
6
2024
pubmed:
29
6
2024
entrez:
29
6
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 38943196
doi: 10.1186/s13195-024-01508-6
pii: 10.1186/s13195-024-01508-6
doi:
Substances chimiques
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)
0
Types de publication
Journal Article
Comparative Study
Letter
Langues
eng
Sous-ensembles de citation
IM
Pagination
141Subventions
Organisme : UCLouvain Action de Recherche Concertée
ID : ARC21/26-114
Organisme : UCLouvain Action de Recherche Concertée
ID : ARC21/26-114
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : ASP40001844
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : CCL40010417
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : FNRS J.0106.22
Organisme : Fonds de la Recherche Fondamentale Stratégique - Walloon Excellence in Life Sciences and Biotechnology
ID : 40010035
Organisme : SAO-FRA Alzheimer's Research Foundation
ID : SAO-FRA 2020/0028
Organisme : SAO-FRA Alzheimer's Research Foundation
ID : SAO-FRA 2018/0025
Informations de copyright
© 2024. The Author(s).
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