Alzheimer s & Dementia· 2026Q1
A murine model of amyloid enhanced tauopathy: progressive changes in tau pathology and behavior
- 1citations
- Q1SCImago
- 2026year
Short summary
Mice engineered with both amyloid precursor protein (APP+PS1) and P301L tau (A/P+P301L) exhibit significantly worse spatial navigation memory deficits compared to mice with only amyloidosis.
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Key points
- A/P+P301L mice show greater spatial navigation memory impairments than control APP+PS1 mice or AAV-tau injected NTg mice.
- Tau phosphorylation and deposition increased progressively from 5 to 9 months post-injection in A/P+P301L mice.
- The model exhibits numerous Gallyas-positive presumptive neurofibrillary tangles.
- Amyloid and tau pathology act synergistically to worsen cognitive impairments.
AI-generated from the title and abstract; the full text is not read.
Abstract
BACKGROUND: Our prior work demonstrated systemic P301L-tau injections in mice with mature amyloid resulted in several-fold enhancement of tauopathy compared to non-transgenic (NTg) littermates. METHODS: APP+PS1 mice were injected intravenously with AAV.CAP-B10 expressing P301L tau (A/P+P301L). Mice were tested behaviorally and tissues collected for measurement of amyloid and tau pathology. RESULTS: A/P+P301L mice have greater spatial navigation memory impairments than control APP+PS1 mice, or AAV-tau injected NTg mice. Tau phosphorylation and deposition increased from 5 to 9 months after injection, culminating in numerous Gallyas-positive presumptive neurofibrillary tangles. DISCUSSION: In this model of amyloid-enhanced tauopathy, tau pathology acts synergistically with amyloidosis to exacerbate cognitive impairments compared to amyloid-only mice. The tauopathy is progressive, with more severe behavioral impairments and neurofibrillary deposits at longer survival times. The temporal staging of pathology in this model resembles that of Alzheimer's disease and may be useful for interrogating the linkage between amyloid and tau pathology.
The authors' abstract, as published at the source. Alzheimer s & Dementia, 2026 · DOI ↗
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Field: Physiology
PhysiologyMedicine