Both N-terminal and C-terminal fragments of Presenilin 1 colocalize with neurofibrillary tangles in neurons and dystrophic neurites of senile plaques in Alzheimer's disease
✍ Scribed by De-Hua Chui; Keiro Shirotani; Hiroshi Tanahashi; Haruhiko Akiyama; Kazuharu Ozawa; Tatsuhide Kunishita; Keikichi Takahashi; Takao Makifuchi; Takeshi Tabira
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 684 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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 NFTbearing SPs and with intraneuronal NFTs in 32% of NFT-bearing neurons. Both antibodies did not detect PHF-tau-positive neuropil threads and A 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 NFTbearing neurons and dystrophic neurites in SPs; both are the pathologic hallmarks of AD.