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Transgenic mouse models based on coexpression of familial AD-associated presenilin and amyloid precursor protein variants successfully mimic characteristic pathological features of AD, including plaque formation, synaptic dysfunction, and loss of memory. Presenilins function as the catalytic subunit of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b3<\/mml:mi>\n                    <\/mml:math>\n                    -secretase, the enzyme that catalyzes intramembraneous proteolysis of amyloid precursor protein to release\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b2<\/mml:mi>\n                    <\/mml:math>\n                    -amyloid peptides. Familial AD-associated mutations in presenilins alter the site of\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b3<\/mml:mi>\n                    <\/mml:math>\n                    -secretase cleavage in a manner that increases the generation of longer and highly fibrillogenic\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b2<\/mml:mi>\n                    <\/mml:math>\n                    -amyloid peptides. In addition to amyloid precursor protein,\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b3<\/mml:mi>\n                    <\/mml:math>\n                    -secretase catalyzes intramembrane proteolysis of many other substrates known to be important for synaptic function. This paper focuses on how various animal models have enabled us to elucidate the physiological importance of diverse\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                      <mml:mi>\u03b3<\/mml:mi>\n                    <\/mml:math>\n                    -secretase substrates, including amyloid precursor protein and discusses their roles in the context of cellular signaling and synaptic function.\n                  <\/jats:p>","DOI":"10.4061\/2010\/825918","type":"journal-article","created":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T02:21:53Z","timestamp":1279678913000},"page":"1-11","source":"Crossref","is-referenced-by-count":5,"title":["Modeling Presenilin-Dependent Familial Alzheimer's Disease: Emphasis on Presenilin Substrate-Mediated Signaling and Synaptic Function"],"prefix":"10.1155","volume":"2010","author":[{"given":"Ang\u00e8le T.","family":"Parent","sequence":"first","affiliation":[{"name":"Department of 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