biostudies-literatureUnknown15(3)de Sousa DMBIn Alzheimer's disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. Here, we depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaquAging630-649https://www.ebi.ac.uk/biostudies/studies/S-EPMC9970308biostudies-literatureImmune-mediated platelet depletion augments Alzheimer's disease neuropathological hallmarks in APP-PS1 mice.PMC9970308Benedetti AMrowetz HUnger MSAigner LAltendorfer BKniewallner KMde Sousa DMBSchallmoser KfalseImmune-mediated platelet depletion augments Alzheimer's disease neuropathological hallmarks in APP-PS1 mice.In Alzheimer's disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. Here, we depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaqu2023-01-01T00:00:00Z2023 Feb2025-05-29T19:45:06.816Z2025-05-29T19:45:06.816ZS-EPMC99703083673488010.18632/aging.204502