{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:13:55Z","timestamp":1780546435059,"version":"3.54.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["T3-AN-15"],"award-info":[{"award-number":["T3-AN-15"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Recent studies have highlighted the significant role of ADAM17\/TACE (encoded by <jats:italic>ADAM17\/TACE<\/jats:italic>) in the pathogenesis of Alzheimer\u2019s disease (AD). Yet, the relationship between <jats:italic>ADAM17\/TACE<\/jats:italic> gene polymorphisms and AD was less studied. This study aims to analyse the relationship of <jats:italic>ADAM17\/TACE<\/jats:italic> gene polymorphism with the risk, age of onset, neuropsychiatric manifestations, cognitive impairment, and medial temporal lobe atrophy in sporadic AD (sAD). This case\u2013control association study was conducted in an Italian cohort consisting of 297 sAD patients and 316 controls. Seven tag-SNPs were selected and genotyped. Linear and logistic regression analyses were used to assess the association between parameters of interest and the genetic variability of <jats:italic>ADAM17\/TACE<\/jats:italic>. After Bonferroni correction, our findings underscore the complexity of genetic influences of <jats:italic>ADAM17\/TACE<\/jats:italic> on sAD, particularly the roles of rs12692385 in modulating sAD risk and the performance on the Rey Auditory Verbal Learning Test \u2013 delayed recall. In addition, rs13008101 significantly affected the performance on the Clock Drawing Test. Moreover, rs10179642 and rs35280016 were associated with a higher frequency and severity of hallucinations and agitation\/aggression, respectively. These results contribute to a deeper understanding of the genetic underpinnings of sAD and may be useful for examining the risk of developing sAD, assessing cognitive deficits, neuropsychiatric symptoms, and informing new therapeutic strategies and future research targeting <jats:italic>ADAM17\/TACE<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0309631","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T17:58:07Z","timestamp":1746813487000},"page":"e0309631","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic variability in ADAM17\/TACE is associated with sporadic Alzheimer\u2019s disease risk, neuropsychiatric symptoms and cognitive performance on the Rey Auditory Verbal Learning and Clock Drawing 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