Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause of dementia in the elderly. AD pathology is characterized by accumulation of microglia around the beta-amyloid (Aβ) plaques which assumes disease-specific transcriptional signatures, as for the disease-associated microglia (DAM). However, the regulators of microglial phagocytosis are still unknown.

Methods

We isolated Aβ-laden microglia from the brain of 5xFAD mice for RNA sequencing to characterize the transcriptional signature in phagocytic microglia and to identify the key non-coding RNAs capable of regulating microglial phagocytosis. Through spatial sequencing, we show the transcriptional changes of microglia in the AD mouse brain in relation to Aβ proximity.

Results

Finally, we show that phagocytic messenger RNAs are regulated by miR-7a-5p, miR-29a-3p and miR-146a-5p microRNAs and segregate the DAM population into phagocytic and non-phagocytic states.

Discussion

Our study pinpoints key regulators of microglial Aβ clearing capacity suggesting new targets for future therapeutic approaches.

SUBMITTER: Scoyni F 

PROVIDER: S-EPMC10916983 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature