Stabilization of mitochondria-associated endoplasmic reticulum membranes regulates Aβ generation in a three-dimensional neural model of Alzheimer's disease.

ABSTRACT:

Introduction

We previously demonstrated that regulating mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) affects axonal Aβ generation in a well-characterized three-dimensional (3D) neural Alzheimer's disease (AD) model. MAMs vary in thickness and length, impacting their functions. Here, we examined the effect of MAM thickness on Aβ in our 3D neural model of AD.

Methods

We employed fluorescence resonance energy transfer (FRET) or fluorescence-based MAM stabilizers, electron microscopy, Aβ enzyme-linked immunosorbent assay (ELISA), and live-cell imaging with kymography to assess how stabilizing MAMs of different gap widths influence Aβ production and MAM axonal mobility.

Results

Stabilizing tight MAMs (∼6 nm gap width) significantly increased Aβ level

SUBMITTER: Zellmer JC 

PROVIDER: S-EPMC11848173 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature