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

Flavia Scoyni*, Luca Giudice, Mari Anna Väänänen, Nicholas Downes, Paula Korhonen, Xin Yi Choo, Nelli Noora Välimäki, Petri Mäkinen, Nea Korvenlaita, Annemieke J. Rozemuller, Helga E. de Vries, Jose Polo, Tiia A. Turunen, Seppo Ylä-Herttuala, Thomas B. Hansen, Alexandra Grubman, Minna U. Kaikkonen, Tarja Malm*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftAlzheimer's and Dementia
Vol/bind20
Nummer2
Sider (fra-til)954-974
Antal sider21
ISSN1552-5260
DOI
StatusUdgivet - feb. 2024

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