BOTH N-TERMINAL AND C-TERMINAL FRAGMENTS OF PRESENILIN-1 COLOCALIZE WITH NEUROFIBRILLARY TANGLES IN NEURONS AND DYSTROPHIC NEURITES OF SENILE PLAQUES IN ALZHEIMERS-DISEASE

Presenilin 1 (PS1) is a causative gene for chromosome 14-linked famili al Alzheimer's disease, The gene product is known to be cleaved into N -terminal fragments (PS1-N) and C-terminal fragments (PS1-C), To under stand the pathophysiological role of PS1, we conducted immunohistochem ical studies using antibodies specific for PS1-N and PS1-C in sporadic Alzheimer's disease (AD). Both antibodies showed punctuate staining e xclusively in neurons and their processes in both control and AD brain s. 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 dystrophi c neurites in 70% of NFT-bearing SPs and with intraneuronal NFTs in 32 % of NFT-bearing neurons. Both antibodies did not detect PHF-tau-posit ive neuropil threads and A beta amyloid fibrils. The colocalization wa s also found in 33-38% of NFT-bearing neurons in progressive supranucl ear palsy. These results indicate that both PS1-N and PS1-C fragments are deposited in part of NFT-bearing neurons and dystrophic neurites i n SPs; both are the pathologic hallmarks of AD. J, Neurosci, Res. 53:9 9-106, 1998. (C) 1998 Wiley-Liss,Inc.