{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:44:43Z","timestamp":1791247483096,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["DRI\u20103203"],"award-info":[{"award-number":["DRI\u20103203"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022942","name":"Moondance Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022942","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n The Alzheimer's disease protective P522R\n PLCG2<\/jats:italic>\n coding variant (rs72824905) is downstream of TREM2, but how it confers disease protection is poorly understood. Using a\n Plcg2<\/jats:italic>\n \u2010R522 knock\u2010in mouse and\n Plcg2<\/jats:italic>\n \u2010P522 control on both wildtype and Alzheimer's disease\u2010like\n App<\/jats:italic>\n \n NL\u2010G\u2010F<\/jats:italic>\n <\/jats:sup>\n amyloidosis mouse backgrounds, aged mice were assayed for amyloid load, microglial activity, and synaptic integrity. In the absence of Alzheimer's disease\u2010like pathology, the R522 variant increased microglial coverage and was associated with reduced ramification complexity, fewer terminal points, and elevated lysosomal CD68 expression. On the\n App<\/jats:italic>\n \n NL\u2010G\u2010F<\/jats:italic>\n <\/jats:sup>\n background, total amyloid burden was unaffected, but expression of the R522 variant led to increased plaque compaction compared to the P522 common variant. The protective R522 variant was also associated with: enhanced microglial engagement with less compact amyloid plaques; reduced microglial localisation around highly compacted plaques; protection from amyloid\u2010induced synapse loss; and decreased engulfment of synaptic material by microglia. Our data indicate a significant direct PLC\u03b32 role in controlling microglial\u2010plaque interactions and synaptic protection downstream of amyloid deposition, prioritizing it as a therapeutic target, potentially as an adjunct to other approaches, such as those targeting amyloid.\n <\/jats:p>","DOI":"10.1002\/glia.70192","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:43:41Z","timestamp":1782452621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alzheimer's Protection by\n PLC\u03b32<\/scp>\n Compacts Plaques, Redistributes Microglia, and Protects Synapses in\n \n App<\/i>\n \n NL<\/i>\n <\/sup>\n <\/scp>\n \n \u2010G\u2010F<\/i>\n <\/sup>\n Mice"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-2887","authenticated-orcid":false,"given":"Ryan J.","family":"Bevan","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0046-318X","authenticated-orcid":false,"given":"Emily","family":"Maguire","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4524-3740","authenticated-orcid":false,"given":"Eilish","family":"Mackinnon","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0735-4729","authenticated-orcid":false,"given":"Elisa","family":"Salis","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-2550","authenticated-orcid":false,"given":"Thomas","family":"Phillips","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-704X","authenticated-orcid":false,"given":"Elena","family":"Simonazzi","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5475-7891","authenticated-orcid":false,"given":"Marieta","family":"Vassileva","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-186X","authenticated-orcid":false,"given":"Nicholas D.","family":"Allen","sequence":"additional","affiliation":[{"name":"School of Biosciences Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4069-0259","authenticated-orcid":false,"given":"Julie","family":"Williams","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0163-1421","authenticated-orcid":false,"given":"Philip R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at Cardiff Cardiff University Cardiff UK"},{"name":"Systems Immunity Research Institute Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"11","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1001\/archneur.65.11.1509","article-title":"Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly","volume":"65","author":"Aizenstein H. 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