Elevated ganglioside GM2 activator (GM2A) in human brain tissue reduces neurite integrity and spontaneous neuronal activity.

ABSTRACT:

Background

Alzheimer's Disease (AD) affects millions globally, but therapy development is lagging. New experimental systems that monitor neuronal functions in conditions approximating the AD brain may be beneficial for identifying new therapeutic strategies.

Methods

We expose cultured neurons to aqueous-soluble human brain extract from 43 individuals across a spectrum of AD pathology. Multi-electrode arrays (MEAs) and live-cell imaging were used to assess neuronal firing and neurite integrity (NI), respectively, following treatments of rat cortical neurons (MEA) and human iPSC-derived neurons (iN) with human brain extracts.

Results

We observe associations between spontaneous activity and Aβ42:40 levels, between neurite integrity and oligomeric Aβ, and between neurite

SUBMITTER: Hsieh YC 

PROVIDER: S-EPMC9494921 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature