The protective PLCγ2-P522R variant mitigates Alzheimer's disease-associated pathologies by enhancing beneficial microglial functions
Summary
These findings suggest that the PLCγ2-P522R variant exerts protective effects against β-amyloid and neuronal pathologies by increasing microglial responsiveness to β-amyloid plaques in APP/PS1 mice. The changes observed in lipid/fatty acid and mitochondrial metabolism revealed by the omics and metabolic assessments of mouse and human microglial models suggest that the protective effects of the PLCγ2-P522R variant are potentially associated with increased metabolic capacity of microglia. © 2025. The Author(s).
| Authors | Takalo M, Jeskanen H, Rolova T, Kervinen I, Hellén M, Heikkinen S, Koivisto H, Jokivarsi K, Müller SA, Koivumäki EM, Mäkinen P, Juopperi SP, Willman RM, Sinisalo R, Hoffmann D, Jäntti H, Peitz M, Fließbach K, Kuulasmaa T, Natunen T, Kemppainen S, Poutiainen P, Leinonen V, Malm T, Martiskainen H, Ramirez A, Haapasalo A, Lichtenthaler SF, Tanila H, Haass C, Rinne J, Koistinaho J, Hiltunen M |
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| Journal | Journal of neuroinflammation |
| Publication Date | 2025 Mar 5;22(1):64 |
| PubMed | 40038760 |
| PubMed Central | PMC11881468 |
| DOI | 10.1186/s12974-025-03387-6 |