Fig. 2

Immunohistochemical characterization of CatD-KO mice. (A-L) Three-week-old wildtype (WT; top row) and CatD-KO (KO; bottom row) mouse hippocampi stained for hematoxylin and eosin (H&E; A, B), cathepsin D (CatD; C, D), pan-Aβ (Aβ; E, F), ubiquitin (G, H), glial fibrillary acidic protein (GFAP; I, J) and Gallyas silver stain counterstained with eosin (K, L). Note that prominent accumulation of Aβ (F) and ubiquitin (H), along with astrogliosis (J) and abundant silver staining (L), occurs exclusively in CatD-KO mice, primarily in the same cells that show high levels of CatD expression in WT mice (C). Scale bar (L) represents 500 μm and is applicable to images in A-L. Quantification of each staining (except H&E) in different brain regions is provided in Sup Fig. 2. M-S, Comparative analysis of Gallyas silver staining in a 3-week-old CatD-KO mouse (M-Q) versus a 77-year-old Alzheimer disease (AD) human brain (R, S). Note how closely Gallyas silver staining in mouse neurons (Q) resembles the staining of NFTs in human neurons (R), with both featuring prominent perinuclear staining (white arrowheads). Scale bars are 1 mm (M), 500 μm (N), 100 μm (O), 50 μm (P, S) and 20 μm (Q, R)