Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations.

Journal Article (Journal Article)

Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were found to be cleaved into two fragments of NTF and CTF independently of the occurrence of PS-1 mutation in human brains. A small portion of PS-1 was recently found to suffer another processing by caspase-3, an apoptosis-related cysteine protease. In contrast to the recent finding that the Volga-German mutation on presenilin-2 (PS-2) affects the increasing caspase-3 PS-2 fragment, the PS-1 mutation did not cause a significant change in PS-1 fragmentation. We conclude that PS-1 fragmentation and other (probably caspase-3-mediated) digestion following apoptosis occur independently of PS-1 mutations.

Full Text

Duke Authors

Cited Authors

  • Okochi, M; Ishii, K; Usami, M; Sahara, N; Kametani, F; Tanaka, K; Fraser, PE; Ikeda, M; Saunders, AM; Hendriks, L; Shoji, SI; Nee, LE; Martin, JJ; Van Broeckhoven, C; St George-Hyslop, PH; Roses, AD; Mori, H

Published Date

  • November 24, 1997

Published In

Volume / Issue

  • 418 / 1-2

Start / End Page

  • 162 - 166

PubMed ID

  • 9414118

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/s0014-5793(97)01378-1


  • eng

Conference Location

  • England