{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:02:43Z","timestamp":1783947763803,"version":"3.55.0"},"reference-count":103,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T00:00:00Z","timestamp":1583539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008049","name":"Fundaci\u00f3n Banco Santander","doi-asserted-by":"publisher","award":["1.010.924"],"award-info":[{"award-number":["1.010.924"]}],"id":[{"id":"10.13039\/100008049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background. Recent reports point to a nuclear origin of Alzheimer\u2019s disease (AD). Aged postmitotic neurons try to repair their damaged DNA by entering the cell cycle. This aberrant cell cycle re-entry involves chromatin modifications where nuclear Tau and the nuclear lamin are involved. The purpose of this work was to elucidate their participation in the nuclear pathological transformation of neurons at early AD. Methodology. The study was performed in hippocampal paraffin embedded sections of adult, senile, and AD brains at I-VI Braak stages. We analyzed phospho-Tau, lamins A, B1, B2, and C, nucleophosmin (B23) and the epigenetic marker H4K20me3 by immunohistochemistry. Results. Two neuronal populations were found across AD stages, one is characterized by a significant increase of Lamin A expression, reinforced perinuclear Lamin B2, elevated expression of H4K20me3 and nuclear Tau loss, while neurons with nucleoplasmic Lamin B2 constitute a second population. Conclusions. The abnormal cell cycle reentry in early AD implies a fundamental neuronal transformation. This implies the reorganization of the nucleo-cytoskeleton through the expression of the highly regulated Lamin A, heterochromatin repression and building of toxic neuronal tangles. This work demonstrates that nuclear Tau and lamin modifications in hippocampal neurons are crucial events in age-related neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms21051841","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:37:34Z","timestamp":1583732254000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer\u2019s Disease Progression"],"prefix":"10.3390","volume":"21","author":[{"given":"Laura","family":"Gil","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Escuela de Medicina, Universidad \u201cAlfonso X el Sabio\u201d, 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-2468","authenticated-orcid":false,"given":"Sandra A.","family":"Ni\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Chi-Ahumada","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3316-1471","authenticated-orcid":false,"given":"Ildelfonso","family":"Rodr\u00edguez-Leyva","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Central \u201cIgnacio Morones Prieto\u201d, San Luis Potos\u00ed 78290, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Banco de cerebros (Biobanco), Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Bel\u00e9n","family":"Rebolledo","sequence":"additional","affiliation":[{"name":"Banco de cerebros (Biobanco), Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5059-7667","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Arias","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Escuela de Medicina, Universidad \u201cAlfonso X el Sabio\u201d, 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-7063","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Jim\u00e9nez-Capdeville","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/323560a0","article-title":"The nuclear lamina is a meshwork of intermediate-Type filaments","volume":"323","author":"Aebi","year":"1986","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1073\/pnas.0602569103","article-title":"Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging","volume":"103","author":"Shumaker","year":"2006","journal-title":"Proc. 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