Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
11 Jul 2023
11 Jul 2023
Historique:
received:
15
10
2021
accepted:
23
06
2023
revised:
09
06
2023
medline:
12
7
2023
pubmed:
12
7
2023
entrez:
11
7
2023
Statut:
aheadofprint
Résumé
The development of Alzheimer's disease (AD) involves central and peripheral immune deregulation. Gene identification and studies of AD genetic variants of peripheral immune components may aid understanding of peripheral-central immune crosstalk and facilitate new opportunities for therapeutic intervention. In this study, we have identified in a Flanders-Belgian family a novel variant p.E317D in the Toll-like receptor 9 gene (TLR9), co-segregating with EOAD in an autosomal dominant manner. In human, TLR9 is an essential innate and adaptive immune component predominantly expressed in peripheral immune cells. The p.E317D variant caused 50% reduction in TLR9 activation in the NF-κB luciferase assay suggesting that p.E317D is a loss-of-function mutation. Cytokine profiling of human PBMCs upon TLR9 activation revealed a predominantly anti-inflammatory response in contrast to the inflammatory responses from TLR7/8 activation. The cytokines released upon TLR9 activation suppressed inflammation and promoted phagocytosis of Aβ
Identifiants
pubmed: 37433968
doi: 10.1038/s41380-023-02166-0
pii: 10.1038/s41380-023-02166-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Alzheimer's Association
ID : ADSF-21-831212-C
Pays : United States
Informations de copyright
© 2023. The Author(s).
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