biostudies-literatureScoyni FAcademy of FinlandAntti and Tyyne Soininen FoundationInstrumentariumin TiedesäätiöInstrumentarium Science FoundationFramework Programme of the European Union Marie Skłodowska CurieThe Finnish Cultural FoundationSigrid Juselius FoundationKuopio University FoundationSaastamoinen FoundationInkeri and Mauri Vänskä Foundation954-974https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916983biostudies-literatureUnknown20(2)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>Our study pinpoints key regulators of microglial Aβ clearing capacity suggesting new targets for future therapeutic approaches.Alzheimer's & dementia : the journal of the Alzheimer's AssociationAlzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs.PMC10916983740264298071307309328287Grubman AYla-Herttuala SValimaki NNMalm TScoyni FGiudice LVaananen MADownes NTurunen TAChoo XYKorhonen Pde Vries HEKaikkonen MUMakinen PHansen TBRozemuller AJPolo JKorvenlaita NfalseAlzheimer's disease-induced phagocytic microglia express a specific profile of coding and non-coding RNAs.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>Our study pinpoints key regulators of microglial Aβ clearing capacity suggesting new targets for future therapeutic approaches.2024-01-01T00:00:00Z2024 Feb2026-07-05T03:14:21.675Z2026-07-05T03:12:10.189ZS-EPMC109169833782882110.1002/alz.13502