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P3–395: Mean age–of–onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased Aβ42 and decreased Aβ40
Author(s) -
Kumar-Singh Samir,
Theuns Jessie,
Van Broeck Bianca,
Pirici Daniel,
Vennekens Krist'l,
Corsmit Ellen,
Cruts Marc,
Dermaut Bart,
Wang Rong,
Van Broeckhoven Christine
Publication year - 2006
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.2006.05.1665
Subject(s) - psen1 , presenilin , in vitro , mutation , biology , alzheimer's disease , phenotype , microbiology and biotechnology , genetics , gene , medicine , disease
pressed phosphorylated beta-catenin coimmunoprecipitated with LAR in LAR-CHO cells. However, inhibition of PS/gamma-secretase activity significantly diminished LAR-beta-catenin association, indicating that PS/ gamma-secretase directly or indirectly regulates interaction of the two proteins. In summary, our results show that LAR is sequentially cleaved by alfaand PS/gamma-secretases. Alfa-secretase first sheds LAR ectodomain producing LAR-CTFs that are further cleaved by PS/gamma-secretase to generate LICDs. We also show that PS/gamma-secretase-mediated cleavage of LAR regulates its association with phosphorylated beta-catenin. Given that beta-catenin phosphorylation status directly affects cell adhesion, our data therefore suggest an important role for PS/gamma-secretase in the regulation of LAR signaling in cell adhesion or synapse formation by releasing LICD.