Chronic P2Y1R inhibition has no effects on gliosis, plaque load, and amyloid metabolism. (A–M) MRS2179 (in comparison to vehicle; n = 6 mice for each group; age of both groups, 9 mo) had no effect on reactive astrogliosis (anti-GFAP) or microgliosis (anti-Iba1). Similarly, no effects were seen on Aβ plaque load and size (IC16 staining) or the density of thioflavin-positive Aβ plaques (P > 0.05, Mann–Whitney test for all comparisons). Cortex (CX) and hippocampus (HC) were investigated separately. Bars, 200 µm. Veh, vehicle-treated. (N and O) Electrochemiluminescence ELISA after sequential extraction from whole-brain homogenates using RIPA and SDS buffer revealed no difference in soluble and insoluble Aβ_1–42 and Aβ_1–40 between APPPS1 mice treated with MRS2179 or vehicle (n = 6 mice for each group; P > 0.05, Mann–Whitney test for all comparisons). (P–T) Densitometric quantification of the Aβ-degrading enzyme neprilysin/CD10, APP, and CTFs normalized to β-actin showed similar expression in MRS2179-treated and vehicle-treated APPPS1 mice (n = 6 mice for each group; P > 0.05, Mann–Whitney test for all comparisons). All data are represented as mean ± SEM.