Presenilin 1 (PS1) is a causative gene for chromosome 14‐linked familial Alzheimer's disease. The gene product is known to be cleaved into N‐terminal fragments (PS1‐N) and C‐terminal fragments (PS1‐C). To understand the pathophysiological role of PS1, we conducted immunohistochemical studies using antibodies specific for PS1‐N and PS1‐C in sporadic Alzheimer's disease (AD). Both antibodies showed punctuate staining exclusively in neurons and their processes in both control and AD brains. PS1‐N immunolabeling colocalized with neurofibrillary tangles (NFTs) in 36% of NFT‐bearing neurons and with dystrophic neurites in 28% of senile plaques (SPs). PS1‐C immunolabeling colocalized with dystrophic neurites in 70% of NFT‐bearing SPs and with intraneuronal NFTs in 32% of NFT‐bearing neurons. Both antibodies did not detect PHF‐tau‐positive neuropil threads and Aβ amyloid fibrils. The colocalization was also found in 33–38% of NFT‐bearing neurons in progressive supranuclear palsy. These results indicate that both PS1‐N and PS1‐C fragments are deposited in part of NFT‐bearing neurons and dystrophic neurites in SPs; both are the pathologic hallmarks of AD. J. Neurosci. Res. 53:99–106, 1998. © 1998 Wiley‐Liss, Inc.