A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch

Zareen Amtul, Patrick A. Lewis, Sian Piper, Richard Crook, Matt Baker, Kirk Findlay, Andrew Singleton, Marion Hogg, Linda Younkin, Steven G Younkin, John Hardy, Michael Hutton, Bradley F Boeve, David Tang-Wai, Todd E. Golde

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Abstract

A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia phenotype has been identified (E. A. Rogaeva et al., 2001, Neurology 57, 621-625). This mutation does not increase Aβ42 levels, but instead acts as dominant negative presenilin, decreasing amyloid β protein (Aβ) production by inhibiting γ-secretase cleavage of the Aβ precursor. The distinct clinical phenotype associated with this mutation suggests that chronic partial inhibition of γ-secretase activity may result in neurodegeneration.

Original languageEnglish (US)
Pages (from-to)269-273
Number of pages5
JournalNeurobiology of Disease
Volume9
Issue number2
DOIs
StatePublished - 2002

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Presenilin-1
Frontotemporal Dementia
Amyloid Precursor Protein Secretases
Dementia
Mutation
Presenilins
Phenotype
Serum Amyloid A Protein
Neurology

ASJC Scopus subject areas

  • Neurology

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A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch. / Amtul, Zareen; Lewis, Patrick A.; Piper, Sian; Crook, Richard; Baker, Matt; Findlay, Kirk; Singleton, Andrew; Hogg, Marion; Younkin, Linda; Younkin, Steven G; Hardy, John; Hutton, Michael; Boeve, Bradley F; Tang-Wai, David; Golde, Todd E.

In: Neurobiology of Disease, Vol. 9, No. 2, 2002, p. 269-273.

Research output: Contribution to journalArticle

Amtul, Z, Lewis, PA, Piper, S, Crook, R, Baker, M, Findlay, K, Singleton, A, Hogg, M, Younkin, L, Younkin, SG, Hardy, J, Hutton, M, Boeve, BF, Tang-Wai, D & Golde, TE 2002, 'A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch', Neurobiology of Disease, vol. 9, no. 2, pp. 269-273. https://doi.org/10.1006/nbdi.2001.0473
Amtul, Zareen ; Lewis, Patrick A. ; Piper, Sian ; Crook, Richard ; Baker, Matt ; Findlay, Kirk ; Singleton, Andrew ; Hogg, Marion ; Younkin, Linda ; Younkin, Steven G ; Hardy, John ; Hutton, Michael ; Boeve, Bradley F ; Tang-Wai, David ; Golde, Todd E. / A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch. In: Neurobiology of Disease. 2002 ; Vol. 9, No. 2. pp. 269-273.
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