Intraneuronal Aβ accumulation causes tau hyperphosphorylation via endolysosomal leakage.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is characterized by amyloid beta (Aβ) peptide plaques and intracellular neurofibrillary tangles formed by hyperphosphorylated tau. Many attempts have been made to clarify the link between Aβ and tau in the pathogenesis, but conclusive data describing a pathway for this connection are still lacking.

Methods

We developed a neuronal model of Aβ-induced toxicity and studied downstream effects of intraneuronal Aβ42 accumulation on tau hyperphosphorylation using confocal microscopy and live cell imaging.

Results

Aβ42 added to the medium was endocytosed into neurons, inducing the formation of endolysosomal protofibrils and endolysosomal leakage, which in turn promoted tau hyperphosphorylation. Asparaginyl endopeptidase (AEP) was released

SUBMITTER: Gao Y 

PROVIDER: S-EPMC11947758 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature