Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.
Nat Commun
; 15(1): 202, 2024 Jan 03.
Article
em En
| MEDLINE
| ID: mdl-38172114
ABSTRACT
In Alzheimer's disease, amyloid-beta (Aß) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aß induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity. We therefore tested whether Aß-related GAP-43 increases, as a marker of synaptic changes, drive tau spreading in 93 patients across the aging and Alzheimer's spectrum with available CSF GAP-43, amyloid-PET and longitudinal tau-PET assessments. We found that (1) higher GAP-43 was associated with faster Aß-related tau accumulation, specifically in brain regions connected closest to subject-specific tau epicenters and (2) that higher GAP-43 strengthened the association between Aß and connectivity-associated tau spread. This suggests that GAP-43-related synaptic changes are linked to faster Aß-related tau spread across connected regions and that synapses could be key targets for preventing tau spreading in Alzheimer's disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Disfunção Cognitiva
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article