Language
English
Publication Date
5-1-2025
Journal
Alzheimer's & Dementia
DOI
10.1002/alz.70238
PMID
40346706
PMCID
PMC12064415
PubMedCentral® Posted Date
5-9-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Introduction: Tau is essential for amyloid beta (Aβ)-induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral amyloid angiopathy (CAA), a major vascular contributor to cognitive decline, affects over 90% of patients with AD. This study explores the impact of tau downregulation on CAA pathogenesis.
Methods: We crossed the Familial Danish Dementia mouse model (Tg-FDD), which develops vascular amyloid, with tau-null (mTau-/-) mice to generate a CAA model lacking endogenous tau (Tg-FDD/mTau-/-). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed.
Results: Tau depletion ameliorated motor and synaptic impairments, reduced vascular amyloid deposition, and prevented vascular damage. Tau ablation also mitigated astrocytic reactivity and neuroinflammation associated with vascular amyloid accumulation.
Conclusion: These findings provide the first in vivo evidence of the beneficial effects of tau downregulation in a CAA mouse model, supporting tau reduction as a potential therapeutic strategy for patients with parenchymal and vascular amyloid deposition.
Highlights: Tau ablation improves motor function and synaptic impair, reduces cerebrovascular amyloid deposits, and prevents vascular damage in a mouse model of cerebral amyloid angiopathy (CAA). Tau reduction decreases astrocytic reactivity, alters neuroinflammatory gene expression, and enhances oligodendrocyte function, suggesting a protective role against neuroinflammation in CAA. These findings highlight tau reduction as a potential therapeutic strategy to mitigate CAA-induced pathogenesis, with implications for treating patients with both parenchymal and vascular amyloid deposition.
Keywords
Animals, Cerebral Amyloid Angiopathy, Disease Models, Animal, Mice, tau Proteins, Mice, Transgenic, Amyloid beta-Peptides, Brain, Mice, Knockout, cerebral amyloid angiopathy, neuroinflammation, tau, vascular amyloid
Published Open-Access
yes
Recommended Citation
Jury-Garfe, Nur; Chimal-Juárez, Enrique; Patel, Henika; et al., "Tau Depletion Diminishes Vascular Amyloid-Related Deficits in a Mouse Model of Cerebral Amyloid Angiopathy" (2025). Faculty, Staff and Students Publications. 6281.
https://digitalcommons.library.tmc.edu/baylor_docs/6281