Figure 1
Pathological signatures of AD occur in cognitively intact individuals (NDAN). (A) Immunohistochemical detection shows reactivity for Aβ plaques (top row) and phosphorylated tau (bottom row) in the dentate gyrus of individuals classifed as control (Braak 1, Plaque 3, MMSE 30), AD (Braak 6, Plaque 1, MMSE 2), or NDAN (Braak 6, Plaque 1, MMSE 27). DAPI-containing mounting medium was used to visualize nuclei (blue). 20x magnification, scale bar 100 μm. (B) Bielschowsky staining in the hippocampus of an NDAN individual shows plaques (thin arrows) and neurofibrillary tangles (thick arrows). (C) An ELISA shows increased Aβ1-42 in AD and NDAN hippocampi (n = 3 per group and asterisks (*) denote values significantly higher than control with p < 0.05). (D) Representative Western blot of soluble hippocampal fractions (300 μg) from individual cases probed with 6e10 shows that LMW Aβ species are present in both AD and NDAN. Densitometric analysis (F) of the major bands (monomer at 4kD and dimer at 8.5kD) together shows that AD and NDAN cases are significantly different than control where the average optical density is set at 100; the asterisks (*) denote statistical significance compared to the control value (p = 0.022, ANOVA); The Western blot shown is representative of 9–10 individual cases assayed in each group and experiments were repeated 3 – 4 times