Common mouse models of tauopathy reflect early but not late human disease.

ABSTRACT:

Background

Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level.

Methods

We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation.

Results

Both mouse models ac

SUBMITTER: Wenger K 

PROVIDER: S-EPMC9893608 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature