Earlier Alzheimer's disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 08 2022
20 08 2022
Historique:
received:
22
09
2021
accepted:
08
08
2022
entrez:
20
8
2022
pubmed:
21
8
2022
medline:
24
8
2022
Statut:
epublish
Résumé
In Alzheimer's disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.
Identifiants
pubmed: 35987901
doi: 10.1038/s41467-022-32592-7
pii: 10.1038/s41467-022-32592-7
pmc: PMC9392750
doi:
Substances chimiques
Amyloid beta-Peptides
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4899Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2022. The Author(s).
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