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To model Alzheimer\u2019s disease and other tauopathies, it is essential that alternative splicing of the <jats:italic>MAPT<\/jats:italic> transcript in these neurons produces the relevant tau isoforms. Human neurons derived from induced pluripotent stem cells, however, express tau isoform compositions characteristic of foetal neurons rather than of adult neurons unless cultured in vitro for extended time periods. In this study, we characterised the dynamics of the <jats:italic>MAPT<\/jats:italic> and <jats:italic>APP<\/jats:italic> alternative splicing during a developmental time-course of porcine and murine cerebral cortices. We found age-dependent and species-specific isoform composition of <jats:italic>MAPT<\/jats:italic>, including 3R and 4R isoforms in the porcine adult brain similar to that of the adult human brain. We converted adult and embryonic fibroblasts directly into induced neurons and found similar developmental patterns of isoform composition, notably, the 3R and 4R isoforms relevant to the pathogenesis of Alzheimer\u2019s disease. Also, we observed cell-type-specific isoform expression of <jats:italic>APP<\/jats:italic> transcripts during the conversion. The approach was further used to generate induced neurons from transgenic pigs carrying Alzheimer\u2019s disease-causing mutations. We show that such neurons authentically model the first crucial steps in AD pathogenesis.<\/jats:p>","DOI":"10.1007\/s12035-020-02258-w","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T19:12:30Z","timestamp":1610046750000},"page":"2075-2087","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Directly Reprogrammed Neurons Express MAPT and APP Splice Variants Pertinent to Ageing and Neurodegeneration"],"prefix":"10.1007","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5987-2909","authenticated-orcid":false,"given":"Mette","family":"Habekost","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Qvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Denham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida E.","family":"Holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne Lund","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"12","key":"2258_CR1","doi-asserted-by":"publisher","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","volume":"82","author":"CL Masters","year":"1985","unstructured":"Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. 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