Neuronal expression and intracellular localization of presenilins in normal and Alzheimer disease brains

The expression patterns of presenilin 1 (PS1) and presenilin 2 (PS2) in human normal and Alzheimer disease (AD) brains were investigated using antibodies to specific N-terminal peptides of PS1 (Alzh14A and Alzh14B) and PS2 (Alzh1A-AB). The antibodies to peptides Alzh14A (Alzh14A-AB) and Alzh14B (Alzh14B-AB) detected the full-length protein (similar to 63 kDa) and the N-terminal-processed fragment (36 kDa) of PS1, while the Alzh1A-AB detected mainly the N-terminal-processed fragment (36 kDa) of PS2. Immunofluorescent staining detected by confocal microscopy suggested that both native PS1 and PS2 are localized mainly in the Golgi/ER apparatus. Immunohistochemical studies of human temporal lobes from 2 normal and 5 sporadic Alzheimer brains revealed high levels of PS1 and PS2 expression in the granule cell layer and pyramidal neurons of the hippocampus. Strong immunoreactivity was found in reactive astrocytes and neurofibrillary tangles of all 5 Alzheimer brains. In contrast, only 2 sporadic Alzheimer brains showed presenilin-positive neuritic plaques. These observations suggest that presenilins may be involved in the pathology of some cases of sporadic AD.