Loss of Aβ43 Production Caused by Presenilin-1 Mutations in the Knockin Mouse Brain.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 8809320 Publication Model: Print Cited Medium: Internet ISSN: 1097-4199 (Electronic) Linking ISSN: 08966273 NLM ISO Abbreviation: Neuron Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, Mass. : Cell Press, c1988-
    • Subject Terms:
      Gene Knock-In Techniques* ; Mutation*; Amyloid beta-Peptides/*metabolism ; Peptide Fragments/*metabolism ; Presenilin-1/*genetics; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/biosynthesis ; Animals ; Brain/metabolism ; Homozygote ; Mice ; Peptide Fragments/biosynthesis
    • Abstract:
      We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer's disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1(-/-) mice. Production and steady-state levels of Aβ40 and Aβ42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the Aβ42/Aβ40 ratio is slightly increased in KI/+ brains. Moreover, the FAD mutation impairs synaptic function, learning and memory, and age-dependent neuronal survival in the adult brain. Here we extend our analysis of the effects of the L435F and C410Y mutations to the generation of Aβ43. Similar to Aβ40 and Aβ42, production of Aβ43 is undetectable in KI/KI brains and reduced in KI/+ brains. These results support our previous conclusions that the L435F and C410Y mutations cause loss of Presenilin function and γ-secretase activity, including impaired Aβ production in the brain. This Matters Arising Response paper addresses the Veugelen et al. (2016) Matters Arising paper, published concurrently in Neuron.
      (Copyright © 2016 Elsevier Inc. All rights reserved.)
    • Comments:
      Comment on: Neuron. 2015 Mar 4;85(5):967-81. (PMID: 25741723)
      Comment on: Neuron. 2016 Apr 20;90(2):410-6. (PMID: 27100199)
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    • Grant Information:
      R01 NS075346 United States NS NINDS NIH HHS; R01 NS042818 United States NS NINDS NIH HHS; RF1 NS041783 United States NS NINDS NIH HHS; R01 NS041783 United States NS NINDS NIH HHS; K24 NS093185 United States NS NINDS NIH HHS
    • Accession Number:
      0 (Amyloid beta-Peptides)
      0 (Peptide Fragments)
      0 (Presenilin-1)
      0 (amyloid beta-protein (1-43))
      0 (presenilin 1, mouse)
      EC 3.4.- (Amyloid Precursor Protein Secretases)
    • Publication Date:
      Date Created: 20160422 Date Completed: 20170619 Latest Revision: 20220512
    • Publication Date:
      20231215
    • Accession Number:
      PMC4840410
    • Accession Number:
      10.1016/j.neuron.2016.03.009
    • Accession Number:
      27100200