Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms.

ABSTRACT:

Introduction

Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.

Methods

We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).

Results

Dynamin inhibition decreased microglial endocytosis of all tested tau species. Meanwhile, HSPG antagonism blocked only fibril uptake, and LRP1 antagonism or genetic dep

SUBMITTER: Falkon KF 

PROVIDER: S-EPMC11848386 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature