Alzheimer's Disease-induced Phagocytic Microglia Express a Specific Profile of Coding and Non-coding RNAs

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2023 Oct 13

PMID 37828821

Authors

Flavia Scoyni

Luca Giudice

Mari-Anna Vaananen

Nicholas Downes

Paula Korhonen

Xin Yi Choo

Nelli-Noora Valimaki

Petri Makinen

Nea Korvenlaita

Annemieke J Rozemuller

Helga E de Vries

Jose Polo

Tiia A Turunen

Seppo Yla-Herttuala

Thomas B Hansen

Alexandra Grubman

Minna U Kaikkonen

Tarja Malm

Affiliations

Soon will be listed here.

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.

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