Aβ 1 16

Immunohistochemistry was performed as described previously^{48 (link)}, with minor modifications. Briefly, 30 µm coronal sections were mounted on glass slides (Menzel Gläser, Superfrost Plus, Thermo Scientific) and stained with 6E10 (1:500, mouse, Aβ 1–16, BioLegend) and Iba1 (1:300, rabbit, Wako). Secondary antibodies were anti-mouse (1:1000, wavelength 555, Alexa Fluor, Invitrogen) and anti-rabbit (1:1000, wavelength 488, Alexa Fluor, Life Technologies). The cortex (parietal association region together with the somatosensory region) and hippocampus (dentate gyrus (DG) and cornu ammonis 2 and 3 (CA2 and CA3) were analyzed in three sections per brain using an epifluorescence microscope (Olympus BX43, LRI, SE, Nikon Eclipse 80i). The number of microglia, amyloid plaques and plaque-associated microglia were analyzed using FIJI (ImageJ) software. Plaque associated microglia were defined as microglia (Iba1+) either co-localizing with the plaque (6E10+) or localized around/next to the plaque. Thioflavin-S staining and analysis were performed as described previously^{46 (link)} and in Supplementary Methods.

Western blots were used to analyze the amount of amyloid oligomers and tetramers in the hippocampus S3 fraction, containing smaller amyloid aggregates. The western blots were performed as previously described^{48 (link)} with the addition of a 5 min membrane incubation in boiling PBS after the transference. Membranes were stained for 6E10 (1:5000, mouse, Aβ 1–16, BioLegend) and secondary anti-mouse (1:10,000, Peroxidase Vector laboratories). Membranes were developed using the ECL clarity developing kit (BioRad) following the manufacturer’s instructions.