Asp664 cleavage in human hippocampus. a, Representative low-magnification (100X) confocal images of hippocampal sections from patients at the indicated ages, stained with APPNeo and counterstained with TOTO-3 to visualize nuclei. Braak stages are denoted for AD cases. b and c, Total areas of APPNeo immunoreactivity in non-diseased and AD human samples were quantified as described in Methods. b, Left panel, averages ± SEM of young (20−45 Y) and aged (68−90 Y) are shown. Right panel, averages ± SEM of the indicated ages are shown. c, Total area of APPNeo immunoreactivity in control and AD groups. d, Total area of APPNeo immunoreactivity in different Braak stage groups within the AD group were compared to controls. Averages ± SEM are shown. AD, no break stage specified. e, Representative low-magnification confocal image of APPNeo-immunostained hippocampus in a 23 Y patient. TOTO-3 was used to counterstain nuclei. f, Representative high-magnification confocal images of CA3 hilus (a and b) and ML granular layer (c and d) in young (a and c) and aged (b and d) non-diseased human brains. g, Lysates from tissue samples obtained from the indicated groups were separated electrophoretically and reacted with the indicated antibodies. ND, non diseased.