Testing the link between isoaspartate and Alzheimer's disease etiology.
Alzheimer's disease (AD)
aging
blood analysis
deamidation
enzyme-linked immunosorbent assay (ELISA)
human serum albumin (HSA)
in vitro diagnostics
mass spectrometry
protein aggregation
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
24
05
2022
received:
16
12
2021
accepted:
25
05
2022
medline:
17
4
2023
pubmed:
5
8
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (Aβ) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free Aβ (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with Aβ and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of Aβ and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.
Substances chimiques
Isoaspartic Acid
0
Amyloid beta-Peptides
0
tau Proteins
0
Blood Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1491-1502Informations de copyright
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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