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

doi:10.1002/alz.13502

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 for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

3 Citations (Scopus)

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.

Original language	English
Journal	Alzheimer's and Dementia
Volume	20
Issue	2
Pages (from-to)	954-974
Number of pages	21
ISSN	1552-5260
DOIs	https://doi.org/10.1002/alz.13502
Publication status	Published - Feb 2024

Keywords

Alzheimer's disease
microglia
microRNAs
phagocytosis
post-transcriptional regulation

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Scoyni, F., Giudice, L., Väänänen, M. A., Downes, N., Korhonen, P., Choo, X. Y., Välimäki, N. N., Mäkinen, P., Korvenlaita, N., Rozemuller, A. J., de Vries, H. E., Polo, J., Turunen, T. A., Ylä-Herttuala, S., Hansen, T. B., Grubman, A., Kaikkonen, M. U., & Malm, T. (2024). Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs. Alzheimer's and Dementia, 20(2), 954-974. https://doi.org/10.1002/alz.13502

@article{606ee5df8f52499280aadba08ca74701,

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, microglia, microRNAs, phagocytosis, post-transcriptional regulation",

author = "Flavia Scoyni and Luca Giudice and V{\"a}{\"a}n{\"a}nen, {Mari Anna} and Nicholas Downes and Paula Korhonen and Choo, {Xin Yi} and V{\"a}lim{\"a}ki, {Nelli Noora} 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",

year = "2024",

month = feb,

doi = "10.1002/alz.13502",

language = "English",

volume = "20",

pages = "954--974",

journal = "Alzheimer's and Dementia",

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Scoyni, F, Giudice, L, Väänänen, MA, Downes, N, Korhonen, P, Choo, XY, Välimäki, NN, Mäkinen, P, Korvenlaita, N, Rozemuller, AJ, de Vries, HE, Polo, J, Turunen, TA, Ylä-Herttuala, S, Hansen, TB, Grubman, A, Kaikkonen, MU & Malm, T 2024, 'Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs', Alzheimer's and Dementia, vol. 20, no. 2, pp. 954-974. https://doi.org/10.1002/alz.13502

Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs. / Scoyni, Flavia; Giudice, Luca; Väänänen, Mari Anna et al.
In: Alzheimer's and Dementia, Vol. 20, No. 2, 02.2024, p. 954-974.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Alzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs

AU - Scoyni, Flavia

AU - Giudice, Luca

AU - Väänänen, Mari Anna

AU - Downes, Nicholas

AU - Korhonen, Paula

AU - Choo, Xin Yi

AU - Välimäki, Nelli Noora

AU - Mäkinen, Petri

AU - Korvenlaita, Nea

AU - Rozemuller, Annemieke J.

AU - de Vries, Helga E.

AU - Polo, Jose

AU - Turunen, Tiia A.

AU - Ylä-Herttuala, Seppo

AU - Hansen, Thomas B.

AU - Grubman, Alexandra

AU - Kaikkonen, Minna U.

AU - Malm, Tarja

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - microglia

KW - microRNAs

KW - phagocytosis

KW - post-transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=85173856636&partnerID=8YFLogxK

U2 - 10.1002/alz.13502

DO - 10.1002/alz.13502

M3 - Journal article

C2 - 37828821

AN - SCOPUS:85173856636

SN - 1552-5260

VL - 20

SP - 954

EP - 974

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 2

ER -

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

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