Dysfunction of the retromer complex system contributes to amyloid and tau pathology in a stem cell model of Down syndrome.

ABSTRACT:

Introduction

Retromer complex proteins are decreased in Down syndrome (DS) brains and correlate inversely with brain amyloidosis. However, whether retromer dysfunction contributes to the amyloid beta (Aβ) and tau neuropathology of DS remains unknown.

Methods

Human trisomic induced Pluripotent Stem Cells (iPSCs) and isogenic controls were differentiated into forebrain neurons, and changes in retromer proteins, tau phosphorylated epitopes, and Aβ levels were assessed in euploid and trisomic neurons using western blot and enzyme-linked immunosorbent assay (ELISA). Genetic overexpression and pharmacological retromer stabilization were used to determine the functional role of the retromer complex system in modulating amyloid and tau pathology.

Results

Trisomic neurons deve

SUBMITTER: Curtis ME 

PROVIDER: S-EPMC9322819 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature