@article{adc7ed82354b4edc9d4de4799fa6588a,
title = "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.",
keywords = "Alzheimer's disease, microRNAs, microglia, phagocytosis, post-transcriptional regulation",
author = "Flavia Scoyni and Luca Giudice and Mari-Anna V{\"a}{\"a}n{\"a}nen and Nicholas Downes and Paula Korhonen and Choo, {Xin Yi} and Nelli-Noora V{\"a}lim{\"a}ki and Petri M{\"a}kinen and Nea Korvenlaita and Rozemuller, {Annemieke J.} and {de Vries}, {Helga E.} and Jose Polo and Turunen, {Tiia A.} and Seppo Yl{\"a}-Herttuala and Hansen, {Thomas B.} and Alexandra Grubman and Kaikkonen, {Minna U.} and Tarja Malm",
note = "Funding Information: The authors acknowledge Mirka Tikkanen for her technical assistance with the brain slices preparation for spatial sequencing, Mireia Gomez‐Budia for the technical assistance in the live imaging experiments, the MHTP Medical Genomics Facility, the Lab Animal Centre at the University of Eastern Finland and Biocenter Kuopio for flow cytometry service. Incucyte live cell imaging and FISH acquisition was carried out with the support of UEF Cell and Tissue Imaging Unit. The illustrations present in this study were created with BioRender.com. This project was supported by Horizon 2020 Framework Programme of the European Union Marie Sk{\l}odowska Curie grant agreement No 740264, Academy of Finland grant agreement No 298071, 307309, 328287, The Finnish Cultural Foundation, Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Instrumentarium Science Foundation, Inkeri and Mauri V{\"a}nsk{\"a} Foundation, Saastamoinen Foundation, Kuopio University Foundation, Antti and Tyyne Soininen Foundation. Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2023",
month = oct,
day = "12",
doi = "https://doi.org/10.1002/alz.13502",
language = "English",
journal = "Alzheimer's & dementia : the journal of the Alzheimer's Association",
issn = "1552-5260",
publisher = "Elsevier Inc.",
}