{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:24:13Z","timestamp":1762543453850,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione","award":["D.G.R. n. 2117 of  21.11.2018"],"award-info":[{"award-number":["D.G.R. n. 2117 of  21.11.2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in the PSEN1 gene are the most common cause of autosomal dominant Alzheimer\u2019s disease, and are characterized by a high phenotype variability. This study describes a five-generation family, with a prevalent late-onset of the disease and a high frequency of depression, in which a new missense mutation (c.789T &gt; G, p.Cys263Trp) in exon 8 of the PSEN1 gene was found. Only the proband presented an early onset at the age of 45 with attention deficit, followed by spatial disorientation, psychiatric symptoms and parkinsonian signs. The other two cases had a late onset of the disease and a typical presentation with memory loss. Both were characterized by a high level of anxiety and depression. The disease course was different with signs of Lewy body dementia for the proband\u2019s mother, and pyramidal involvement and a shorter disease duration for the proband\u2019s maternal aunt. The other eight cases with late-onset dementia and three cases with a long history of depression have been reported in the family pedigree, underlying the high phenotype variability of PSEN1 mutations.<\/jats:p>","DOI":"10.3390\/ijms22126215","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T04:22:22Z","timestamp":1623212542000},"page":"6215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A New Presenilin 1 (Psen1) Mutation (p.Cys263Trp) as a Cause of Both Early and Late-Onset Alzheimer\u2019s Disease in a Large Italian Family"],"prefix":"10.3390","volume":"22","author":[{"given":"Rosanna","family":"Tortelli","sequence":"first","affiliation":[{"name":"Center for Neurodegenerative Diseases and the Aging Brain, University of Bari \u201cAldo Moro\u201d\u2014A.O. Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Seripa","sequence":"additional","affiliation":[{"name":"Complex Unit of Geriatrics, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"},{"name":"Laboratory for Advanced Hematological Diagnostics, Department of Hematology and Stem Cell Transplant, \u201cVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Zecca","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Diseases and the Aging Brain, University of Bari \u201cAldo Moro\u201d\u2014A.O. Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Dell\u2019Abate","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Diseases and the Aging Brain, University of Bari \u201cAldo Moro\u201d\u2014A.O. Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-9714","authenticated-orcid":false,"given":"Paola","family":"Bisceglia","sequence":"additional","affiliation":[{"name":"Complex Unit of Geriatrics, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria","family":"Barulli","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Diseases and the Aging Brain, University of Bari \u201cAldo Moro\u201d\u2014A.O. Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"De Blasi","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Diseases and the Aging Brain, University of Bari \u201cAldo Moro\u201d\u2014A.O. Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy"},{"name":"Department of Radiology, \u201cPia Fondazione Cardinale G. Panico\u201d, 73039 Tricase, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Logroscino","sequence":"additional","affiliation":[{"name":"Department of Radiology, \u201cPia Fondazione Cardinale G. Panico\u201d, 73039 Tricase, Italy"},{"name":"Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari \u2018Aldo Moro\u2019, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","unstructured":"GBD 2016 Demmentia Collaborators (2019). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. 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