The protective PLCγ2-P522R variant mitigates Alzheimer’s disease-associated pathologies by enhancing beneficial microglial functions
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.
Authors
- Tarja Malm (ORCID: https://orcid.org/0000-0002-9530-7472)
- Kimmo Jokivarsi
- Marianna Hellén
- Mari Takalo (ORCID: https://orcid.org/0000-0002-6609-1860)
- Michael Peitz (ORCID: https://orcid.org/0000-0001-5777-4240)
- Annakaisa Haapasalo (ORCID: https://orcid.org/0000-0003-0959-2957)
- Susanna Kemppainen (ORCID: https://orcid.org/0000-0001-5372-1918)
- Heli Jeskanen (ORCID: https://orcid.org/0009-0002-4783-7951)
- Dorit Hoffmann
- Pekka Poutiainen (ORCID: https://orcid.org/0000-0001-8148-9909)
- Henna Martiskainen (ORCID: https://orcid.org/0000-0003-2796-1859)
- Sami Heikkinen (ORCID: https://orcid.org/0000-0001-6976-2028)
- Alfredo Ramı́rez (ORCID: https://orcid.org/0000-0003-4991-763X)
- Klaus Fließbach (ORCID: https://orcid.org/0000-0002-0183-7510)
- Taisia Rõlova (ORCID: https://orcid.org/0000-0002-8869-593X)
- Ville Leinonen (ORCID: https://orcid.org/0000-0002-8660-5742)
- Henna Jäntti (ORCID: https://orcid.org/0000-0003-3005-407X)
- Teemu Natunen (ORCID: https://orcid.org/0000-0003-1848-2792)
- Teemu Kuulasmaa (ORCID: https://orcid.org/0000-0002-1795-7314)
- Christian Haass (ORCID: https://orcid.org/0000-0002-4869-1627)
- Roosa-Maria Willman (ORCID: https://orcid.org/0009-0009-5249-9038)
- Jari Koıstınaho (ORCID: https://orcid.org/0000-0001-6559-1153)
- Stefan F. Lichtenthaler (ORCID: https://orcid.org/0000-0003-2211-2575)
- Stephan A. Müller (ORCID: https://orcid.org/0000-0003-3414-307X)
- Mikko Hiltunen (ORCID: https://orcid.org/0000-0003-3566-4096)
- Juha O. Rinne (ORCID: https://orcid.org/0000-0001-6369-0764)
- Sini-Pauliina Juopperi
- Inka Kervinen
- Rosa Sinisalo
- Petra Mäkinen
- Esa-Mikko Koivumäki
- Heikki Tanila
- Hennariikka Koivisto
Institutions
- University of Helsinki (FI)
- University of Bonn (DE)
- University of Turku (FI)
- The University of Texas at San Antonio Health Science Center (US)
- University of Eastern Finland (FI)
- University of Cologne (DE)
- University Hospital Bonn (DE)
- German Center for Neurodegenerative Diseases (DE)
- Turku University Hospital (FI)
- TUM Klinikum (DE)
- Kuopio University Hospital (FI)
- Turku PET Centre (FI)
- Institute for Neurodegenerative Disorders (US)
- Munich Cluster for Systems Neurology (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1186/s12974-025-03387-6
- Citations
- 11
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 9.26
Funders
- Alzheimer's Association
- Itä-Suomen Yliopisto
- Academy of Finland
- Biocenter Finland