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These functions are mediated by a broad repertoire of cell-surface receptors, including G protein-coupled receptors such as the ADP receptor P2Y12 and GPR34, a receptor for lysophosphatidylserine. While GPR34 deficiency has been linked to impaired microglial phagocytosis, its regulation in relation to amyloid-\u03b2 (A\u03b2) and tau pathology in Alzheimer\u2019s disease (AD) remains unclear. We performed a quantitative analysis of microglial density, morphology, and GPR34 expression in the medial temporal lobe cortex (MTLC) of elderly human body and tissue donors across the AD spectrum. Using fluorescence in situ hybridization and immunolabeling, we analyzed 187,670 microglial cells and correlated microglial parameters with the severity and spatial proximity of A\u03b2 plaques and tau inclusions. In parallel, we analyzed human single-nucleus RNA sequencing data from 236,002 cells to assess GPR34 expression across microglial subtypes, brain regions, and neuropathological stages. Microglial density and overall morphology in the MTLC were largely preserved, independent of local A\u03b2 or hyperphosphorylated tau burdens. Apart from a moderate shortening of microglial processes in the immediate vicinity of A\u03b2 plaques, no consistent pathology-associated morphological changes were detected. GPR34 expression showed pronounced cell-to-cell variability and differed across microglial subtypes and brain regions, but neither expression intensity nor the proportion of GPR34-positive microglia correlated consistently with Braak stage or Thal phase. These findings suggest that GPR34 regulation in human microglia is highly context-dependent and shaped by regional and cellular heterogeneity rather than AD-associated pathology alone.<\/jats:p>","DOI":"10.1007\/s00401-026-03035-0","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:23:24Z","timestamp":1781522604000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of GPR34 in microglia remains stable in human Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"151","author":[{"given":"Sophie","family":"Seiffer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Rotter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Brendler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Ricken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Detzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Braune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Sch\u00f6neberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Winter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"3035_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031495","volume":"22","author":"ER Abels","year":"2021","unstructured":"Abels ER, Nieland L, Hickman S, Broekman MLD, El Khoury J, Maas SLN (2021) Comparative analysis identifies similarities between the Human and Murine microglial sensomes. 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