Astrocyte reactivity influences amyloid-ß effects on tau pathology in preclinical Alzheimer's disease.
Nat Med
; 29(7): 1775-1781, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37248300
ABSTRACT
An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-ß (Aß)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aß effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aß with tau phosphorylation in CU individuals. We found that Aß was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast+). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aß only in CU Ast+ individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aß with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
/
Cognitive Dysfunction
Type of study:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nat Med
Journal subject:
BIOLOGIA MOLECULAR
/
MEDICINA
Year:
2023
Document type:
Article
Affiliation country:
United States