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O4‐03‐08: The first 3rd generation Alzheimer mouse, PLB1: Design and development
Author(s) -
Platt Bettina,
Riedel Gernot
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.538
Subject(s) - transgene , gene knockin , biology , genetically modified mouse , gene targeting , phenotype , presenilin , microbiology and biotechnology , gene , genetics , alzheimer's disease , medicine , disease , pathology
observed in any Aß-degrading protease knockout mouse studied to date. Remarkably, this increase was selective for Aß42, resulting in elevated Aß42/ Aß40 ratios comparable to those induced by presenilin mutations that cause early-onset AD. Cultured neurons from CatD-KO mice also showed selective defects in the catabolism of Aß42, but not Aß40. Furthermore, relative to age-matched controls, the brains of CatD-KO mice showed pronounced increases in the levels of tau and phosphorylated forms thereof, while showing no increases in the levels of several other cytosolic proteins. Conclusions: Our findings demonstrate that, in vivo, CatD deficiency leads to large and highly selective increases in the two protein species most strongly linked to the pathogenesis of AD_Aß42 and tau. Combined with human molecular genetic data on the CatD gene (CTSD) to be presented at this meeting (Burgess et al.), our findings suggest that CatD plays a protective role in the pathogenesis of AD by mediating the catabolism of Aß42 and tau.