Amyloid-beta antibody binding to cerebral amyloid angiopathy fibrils and risk for amyloid-related imaging abnormalities.
ARIA
Alzheimer’s disease
Amyloid
CAA
Immunotherapy
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 05 2024
13 05 2024
Historique:
received:
22
12
2023
accepted:
08
05
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
Therapeutic antibodies have been developed to target amyloid-beta (Aβ), and some of these slow the progression of Alzheimer's disease (AD). However, they can also cause adverse events known as amyloid-related imaging abnormalities with edema (ARIA-E). We investigated therapeutic Aβ antibody binding to cerebral amyloid angiopathy (CAA) fibrils isolated from human leptomeningeal tissue to study whether this related to the ARIA-E frequencies previously reported by clinical trials. The binding of Aβ antibodies to CAA Aβ fibrils was evaluated in vitro using immunoprecipitation, surface plasmon resonance, and direct binding assay. Marked differences in Aβ antibody binding to CAA fibrils were observed. Solanezumab and crenezumab showed negligible CAA fibril binding and these antibodies have no reported ARIA-E cases. Lecanemab showed a low binding to CAA fibrils, consistent with its relatively low ARIA-E frequency of 12.6%, while aducanumab, bapineuzumab, and gantenerumab all showed higher binding to CAA fibrils and substantially higher ARIA-E frequencies (25-35%). An ARIA-E frequency of 24% was reported for donanemab, and its binding to CAA fibrils correlated with the amount of pyroglutamate-modified Aβ present. The findings of this study support the proposal that Aβ antibody-CAA interactions may relate to the ARIA-E frequency observed in patients treated with Aβ-based immunotherapies.
Identifiants
pubmed: 38740836
doi: 10.1038/s41598-024-61691-2
pii: 10.1038/s41598-024-61691-2
doi:
Substances chimiques
Amyloid beta-Peptides
0
Antibodies, Monoclonal, Humanized
0
bapineuzumab
NC11WKO35D
Amyloid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10868Informations de copyright
© 2024. The Author(s).
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