Abstract
Alzheimers disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid β-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than ∼80% of all FAD mutations. All PSEN1 FAD mutations can increase the Aβ42:Aβ40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of β-secretase-derived secreted form of APP (sAPPβ), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPPβ levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPβ levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPβ.
Keywords: Alzheimer's disease, FAD mutation, APP, PSEN1, N-APP, sAPPβ
Current Alzheimer Research
Title: Familial Alzheimers Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-β Protein Precursor Generated by β-Secretase Cleavage
Volume: 7 Issue: 1
Author(s): C. Zhang, A. Browne, D. Y. Kim and R. E. Tanzi
Affiliation:
Keywords: Alzheimer's disease, FAD mutation, APP, PSEN1, N-APP, sAPPβ
Abstract: Alzheimers disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid β-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than ∼80% of all FAD mutations. All PSEN1 FAD mutations can increase the Aβ42:Aβ40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of β-secretase-derived secreted form of APP (sAPPβ), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPPβ levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPβ levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPβ.
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Cite this article as:
Zhang C., Browne A., Kim Y. D. and Tanzi E. R., Familial Alzheimers Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-β Protein Precursor Generated by β-Secretase Cleavage, Current Alzheimer Research 2010; 7 (1) . https://dx.doi.org/10.2174/156720510790274428
DOI https://dx.doi.org/10.2174/156720510790274428 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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