Evolving prion-like tau conformers differentially alter postsynaptic proteins in neurons inoculated with distinct isolates of Alzheimer's disease tau.

ABSTRACT:

Objectives

Although accumulation of misfolded tau species has been shown to predict cognitive decline in patients with Alzheimer's disease (AD) and other tauopathies but with the remarkable diversity of clinical manifestations, neuropathology profiles, and time courses of disease progression remaining unexplained by current genetic data. We considered the diversity of misfolded tau conformers present in individual AD cases as an underlying driver of the phenotypic variations of AD and progressive loss of synapses.

Methods

To model the mechanism of tau propagation and synaptic toxicity of distinct tau conformers, we inoculated wild-type primary mouse neurons with structurally characterized Sarkosyl-insoluble tau isolates from the frontal cortex of six AD cases and monitored t

SUBMITTER: Hromadkova L 

PROVIDER: S-EPMC10507869 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature