Title: Familial Alzheimer's Disease Mutations in Presenilin Generate Amyloidogenic Ab Peptide Seeds
Authors: Veugelen, Sarah
Saito, Takashi
Saido, Takaomi C
Chavez Gutierrez, Lucia #
De Strooper, Bart # ×
Issue Date: Apr-2016
Publisher: Cell Press
Series Title: Neuron vol:90 issue:2 pages:410-416
Abstract: Recently it was proposed that the familial Alzheimer's disease (FAD) causing presenilin (PSEN) mutations PSEN1-L435F and PSEN1-C410Y do not support the generation of Aβ-peptides from the amyloid precursor protein (APP). This challenges the amyloid hypothesis and disagrees with previous work showing that PSEN1 FAD causing mutations generate invariably long Aβ and seed amyloid. We contrast here the proteolytic activities of these mutant PSEN alleles with the complete loss-of-function PSEN1-D257A allele. We find residual carboxy- and endo-peptidase γ-secretase activities, similar to the formerly characterized PSEN1-R278I. We conclude that the PSEN1-L435F and -C410Y mutations are extreme examples of the previously proposed "dysfunction" of γ-secretase that characterizes FAD-associated PSEN. This Matters Arising paper is in response to Xia et al. (2015), published in Neuron. See also the response by Xia et al. (2016), published in this issue.
ISSN: 0896-6273
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for the Research of Neurodegenerative Diseases
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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