20.500.12556/DiRROS-28598 Population and single-cell analyses reveal immune cell-specific expression profiles associated with Alzheimer's disease risk INTRODUCTION Dysregulation of the peripheral immune system may increase Alzheimer's disease (AD) risk, but the underlying cell type-specific mechanisms remain unclear. METHODS We conducted Mendelian randomization and colocalization analyses of 4489 genes using single-cell expression quantitative trait locus data from unstimulated and stimulated peripheral immune cells, integrated with an AD genome-wide association study (N = 455,258). Spatial transcriptomics of brain tissue samples was used to identify brain-infiltrating immune cells. RESULTS Thirteen genes were associated with AD risk. Expression of BIN1, CTSW, CTSH, HLA-DRB1, TSTD1, PLEKHA1, and SCIMP increased AD risk, while EPHA1-AS1, FCER1G, FIBP, KAT8, STX4, and HLA-DQA1 reduced it. These associations were peripheral immune cell type and state specific. PLEKHA1 and TSTD1 were upregulated and FIBP downregulated in natural killer and T cells in AD brain tissue. DISCUSSION These findings link immune cell-specific gene expression to AD risk across activation states and within brain-infiltrating immune cells, highlighting potential targets for immune-based AD prevention and treatment. imunologija nevrodegenerativne bolezni genetika Alzheimerjeva bolezen true false true Angleški jezik Slovenski jezik Neznano 2026-03-25 11:02:43 2026-03-25 11:02:43 2026-03-27 04:05:18 0000-00-00 00:00:00 2026 0 0 Slovenski soavtorji: Martin Stražar, Hang-Mao Lee, Orr Ashenberg, Nina Mars, Pyry N. Sipilä, Samuli Ripatti, Dan Graham, Mika Kivimäki, Ramnik J. Xavier; Nasl. z nasl. zaslona; Opis vira z dne 25. 3. 2026; str. 1-14 iss. 3, [article no.] e71282 Vol. 22 Mar. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2026-03-22 616.8 1552-5279 10.1002/alz.71282 272963843 https://doi.org/10.1002/alz.71282 1 c682d797-2831-11f1-aa40-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42472 RAZ_Lindbohm_Joni_V._2026.pdf RAZ_Lindbohm_Joni_V._2026.pdf 1 CC684CA3D3A0759E6434488449FCA336 9d4c5817c0cde4d27c9b9ee8aca79af8c66f4f20c05b53865572e7faf04aa8d3 e52622cb-2831-11f1-aa40-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42473 Nacionalni inštitut za biologijo 0 0 0