{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:44:30Z","timestamp":1790919870810,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,5,25]]},"abstract":"<jats:p>\n                    Early-onset familial Alzheimer's disease is the most aggressive form of Alzheimer's, striking patients as early as their 30s; those patients typically carry mutations in\n                    <jats:italic>presenilin-1<\/jats:italic>\n                    and\n                    <jats:italic>presenilin-2<\/jats:italic>\n                    . To investigate the coordinated functions of presenilin in the adult brain, we generated double knockout mice, in which both presenilins were deleted in the forebrain. We found that concurrent loss of presenilins in adulthood resulted in massive cortical shrinkage, atrophy of hippocampal molecular layers and corpus callosum, and enlargement of the lateral and third ventricles. We further revealed that deficiency of presenilins caused a series of biochemical alterations, including neuronal atrophy, astrogliosis, caspase-3-mediated apoptosis, and tau hyperphosphorylation. Thus, our study demonstrates that presenilins are essential for the ongoing maintenance of cortical structures and function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0402733101","type":"journal-article","created":{"date-parts":[[2004,5,17]],"date-time":"2004-05-17T20:54:16Z","timestamp":1084827256000},"page":"8162-8167","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":112,"title":["Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's\n                    <i>presenilin-1<\/i>\n                    and\n                    <i>presenilin-2<\/i>"],"prefix":"10.1073","volume":"101","author":[{"given":"Ruiben","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Shrom","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe Z.","family":"Tsien","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,5,17]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"146","volume":"64","year":"1907","unstructured":"Alzheimer, A. 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