{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:28:01Z","timestamp":1779920881153,"version":"3.53.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Modena and Reggio Emilia","award":["FAR2021INTERM_O_UNIM"],"award-info":[{"award-number":["FAR2021INTERM_O_UNIM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are recognized as part of a disease continuum (FTD-ALS spectrum), in which the most common genetic cause is chromosome 9 open reading frame 72 (C9ORF72) gene hexanucleotide repeat expansion. The clinical phenotype of patients carrying this expansion varies widely and includes diseases beyond the FTD-ALS spectrum. Although a few cases of patients with C9ORF72 expansion and a clinical or biomarker-supported diagnosis of Alzheimer\u2019s disease (AD) have been described, they have been considered too sparse to establish a definite association between the C9ORF72 expansion and AD pathology. Here, we describe a C9ORF72 family with pleomorphic phenotypical expressions: a 54-year-old woman showing cognitive impairment and behavioral disturbances with both neuroimaging and cerebrospinal fluid (CSF) biomarkers consistent with AD pathology, her 49-year-old brother with typical FTD-ALS, and their 63-year-old mother with the behavioral variant of FTD and CSF biomarkers suggestive of AD pathology. The young onset of disease in all three family members and their different phenotypes and biomarker profiles make the simple co-occurrence of different diseases an extremely unlikely explanation. Our report adds to previous findings and may contribute to further expanding the spectrum of diseases associated with C9ORF72 expansion.<\/jats:p>","DOI":"10.3390\/genes14040930","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T02:30:03Z","timestamp":1681785003000},"page":"930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Young Onset Alzheimer\u2019s Disease Associated with C9ORF72 Hexanucleotide Expansion: Further Evidence for a Still Unsolved Association"],"prefix":"10.3390","volume":"14","author":[{"given":"Giulia","family":"Vinceti","sequence":"first","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-0181","authenticated-orcid":false,"given":"Chiara","family":"Gallingani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Zucchi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2566-3671","authenticated-orcid":false,"given":"Ilaria","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-0915","authenticated-orcid":false,"given":"Giulia","family":"Gianferrari","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-2365","authenticated-orcid":false,"given":"Cecilia","family":"Simonini","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bedin","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Chiari","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-9782","authenticated-orcid":false,"given":"Jessica","family":"Mandrioli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1474-4422(12)70043-1","article-title":"Frequency of the C9orf72 Hexanucleotide Repeat Expansion in Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: A Cross-Sectional Study","volume":"11","author":"Majounie","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.tins.2013.04.010","article-title":"Current Insights into the C9orf72 Repeat Expansion Diseases of the FTLD\/ALS Spectrum","volume":"36","author":"Cruts","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.semcdb.2019.06.003","article-title":"ALS and FTD: Where RNA Metabolism Meets Protein Quality 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Alzheimer\u2019s Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/930\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:17:40Z","timestamp":1760123860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/4\/930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["genes14040930"],"URL":"https:\/\/doi.org\/10.3390\/genes14040930","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]}}}