{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:41:19Z","timestamp":1777394479213,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T00:00:00Z","timestamp":1468454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2016,8,8]]},"abstract":"<jats:p>\n                    Mutations in the amyloid-\u03b2 protein precursor gene (\n                    <jats:italic>A\u03b2PP<\/jats:italic>\n                    ), the presenilin 1 gene (\n                    <jats:italic>PSEN1<\/jats:italic>\n                    ) or the presenilin 2 gene (\n                    <jats:italic>PSEN2<\/jats:italic>\n                    ) that increase production of the A\u03b2PP-derived peptide A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    cause early-onset Alzheimer\u2019s disease. Rodent models of the disease show that further increase in A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    production and earlier brain pathology can be obtained by coexpressing\n                    <jats:italic>A\u03b2PP<\/jats:italic>\n                    and\n                    <jats:italic>PSEN1<\/jats:italic>\n                    mutations. To generate such elevated A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    level in a large animal model, we produced G\u00f6ttingen minipigs carrying in their genome one copy of a human\n                    <jats:italic>PSEN1<\/jats:italic>\n                    cDNA with the Met146Ile (\n                    <jats:italic>PSEN1M146I<\/jats:italic>\n                    ) mutation and three copies of a human\n                    <jats:italic>A\u03b2PP695<\/jats:italic>\n                    cDNA with the Lys670Asn\/Met671Leu (\n                    <jats:italic>A\u03b2PPsw<\/jats:italic>\n                    ) double-mutation. Both transgenes were expressed in fibroblasts and in the brain, and their respective proteins were processed normally. Immunohistochemical staining with A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    -specific antibodies detected intraneuronal accumulation of A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    in brains from a 10- and an 18-month-old pig. Such accumulation may represent an early event in the pathogenesis of Alzheimer\u2019s disease.\n                  <\/jats:p>","DOI":"10.3233\/jad-160408","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T12:24:59Z","timestamp":1468585499000},"page":"1617-1630","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":43,"title":["Expression of the Alzheimer\u2019s Disease Mutations\n                    <i>A\u03b2PP695sw<\/i>\n                    and\n                    <i>PSEN1M146I<\/i>\n                    in Double-Transgenic G\u00f6ttingen Minipigs"],"prefix":"10.1177","volume":"53","author":[{"given":"Jannik E.","family":"Jakobsen","sequence":"first","affiliation":[{"name":"Department of Biomedicine (East), Aarhus University, Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne 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