Enhancement of amyloid β 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease

Ohoshi Murayama, Taisuke Tomita, Naomi Nihonmatsu, Miyuki Murayama, Xiaoyan Sun, Toshiyuki Honda, Takeshi Iwatsubo, Akihiko Takashima

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Families bearing mutations in the presenilin 1 (PS1) gene develop early onset familial Alzheimer's disease (FAD). Further, some PS1 mutants enhance secretion of the longer form of amyloid β protein (Aβ42). We constructed cDNAs encoding human PS1 harboring 28 FAD-linked mutations, and examined the effects of the expressed PS1 mutants on Aβ42 secretion in β amyloid precursor producing COS-1 cells. All the mutants significantly enhanced the ratio of Aβ42 to total Aβ compared with wild-type PS1. However, the increase in Aβ42 ratio in cells with each PS1 mutation did not correlate with the reported age of onset of FAD caused by that mutation. These results suggest that increased Aβ42 secretion is important for the development of Alzheimer's disease (AD), but may not be the only factor contributing to the onset of AD.

Original languageEnglish (US)
Pages (from-to)61-63
Number of pages3
JournalNeuroscience Letters
Volume265
Issue number1
DOIs
StatePublished - Apr 9 1999
Externally publishedYes

Fingerprint

Presenilin-1
Amyloid
Alzheimer Disease
Mutation
Amyloidogenic Proteins
COS Cells
Age of Onset
Complementary DNA
Genes

Keywords

  • Aβ1-42
  • Age of onset
  • Familial Alzheimer's disease
  • Mutation
  • Presenilin 1
  • Transfection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Enhancement of amyloid β 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease. / Murayama, Ohoshi; Tomita, Taisuke; Nihonmatsu, Naomi; Murayama, Miyuki; Sun, Xiaoyan; Honda, Toshiyuki; Iwatsubo, Takeshi; Takashima, Akihiko.

In: Neuroscience Letters, Vol. 265, No. 1, 09.04.1999, p. 61-63.

Research output: Contribution to journalArticle

Murayama, O, Tomita, T, Nihonmatsu, N, Murayama, M, Sun, X, Honda, T, Iwatsubo, T & Takashima, A 1999, 'Enhancement of amyloid β 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease', Neuroscience Letters, vol. 265, no. 1, pp. 61-63. https://doi.org/10.1016/S0304-3940(99)00187-1
Murayama, Ohoshi ; Tomita, Taisuke ; Nihonmatsu, Naomi ; Murayama, Miyuki ; Sun, Xiaoyan ; Honda, Toshiyuki ; Iwatsubo, Takeshi ; Takashima, Akihiko. / Enhancement of amyloid β 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease. In: Neuroscience Letters. 1999 ; Vol. 265, No. 1. pp. 61-63.
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