Abstract
Background Tau related pathology is the most reliable predictor of cognitive decline in Alzheimer’s disease. However, it remains unclear by which mechanisms tau contributes to neurodegeneration and neuronal dysfunction. The use of viral vectors provides an effective approach to replicate cardinal features of tauopathies in the mouse brain. AAV vectors were designed for overexpression of various forms of human tau, in order to dissect the mechanisms underlying tau hyperphosphorylation, aggregation and neurotoxicity in vivo.
Highlights
Tau related pathology is the most reliable predictor of cognitive decline in Alzheimer’s disease
Materials and methods We generated Associated Viral (AAV) constructs encoding various forms of the human tau protein, including wild-type (WT) tau, a mutant form causing frontotemporal dementia (P301S) and a tau variant previously reported as aggregationdeficient (I277P/ I308P)
Mice injected with WT and P301S tau-expressing vectors displayed a progressive decline in motor performance, most severe in the P301S mutant
Summary
Tau related pathology is the most reliable predictor of cognitive decline in Alzheimer’s disease. It remains unclear by which mechanisms tau contributes to neurodegeneration and neuronal dysfunction. The use of viral vectors provides an effective approach to replicate cardinal features of tauopathies in the mouse brain. AAV vectors were designed for overexpression of various forms of human tau, in order to dissect the mechanisms underlying tau hyperphosphorylation, aggregation and neurotoxicity in vivo
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