In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds.

ABSTRACT: Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy. MAPT^Int10+3G>A and MAPT^{S305N;Int10+3G>A} lines show abundant hyperphosphorylated tau in the hippocampus and entorhinal cortex, but they do not develop seed-competent fibrillar structures. Accumulation of hyperphosphorylated tau was accompanied by neurite degenerat

SUBMITTER: Watamura N 

PROVIDER: S-EPMC11802456 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature