{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:02:24Z","timestamp":1784343744738,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study investigated the clinicopathological characteristics and molecular spectrum of amyloid\u2010beta (A\u03b2) in unnatural deaths among relatively young individuals with moderate\u2010to\u2010severe A\u03b2 deposition, including cases of early\u2010onset Alzheimer's disease. A total of 856 forensic autopsy cases aged 40\u201369\u2009years were analyzed. Detailed semiquantitative and quantitative immunohistochemical analyses were performed in the neocortex, striatum (caudate nucleus, putamen, and nucleus accumbens [NAc]), and amygdala using antibodies targeting multiple A\u03b2 species (A\u03b238, A\u03b239, A\u03b240, A\u03b242, A\u03b243, pyroglutamate\u2010modified A\u03b2 at the third glutamate residue [A\u03b2Np3E], and serine 8\u2010phosphorylated A\u03b2), as well as phosphorylated tau. Ward's hierarchical cluster analysis was also performed. Thirty\u2010three cases (eight females; 3.9%), including six early\u2010onset Alzheimer's disease cases, were identified. Three cases exhibited genetic abnormalities (one with Down syndrome and two with\n                    <jats:italic>presenilin 1 [PSEN1]<\/jats:italic>\n                    mutations). Marked regional heterogeneity in A\u03b2 molecular profiles was observed, particularly within the striatum. Notably, the NAc displayed a distinct pattern of A\u03b2 deposition and occasional NAc\u2010predominant cerebral amyloid angiopathy. Cases with cognitive impairment (CI) demonstrated more advanced A\u03b2 and tau pathology than CI\u2010negative cases; notably, interstitial A\u03b242 and A\u03b243 burdens were significantly elevated across all regions. Strikingly, siblings carrying the same\n                    <jats:italic>PSEN1<\/jats:italic>\n                    mutation\u2014one with CI and the other without\u2014exhibited divergent pathological patterns. Although suicide accounted for approximately one\u2010third of cases, a higher neocortical A\u03b2 burden was associated with a lower frequency of suicide, and no significant difference in suicide rates was observed compared with cases lacking substantial A\u03b2 deposition. Cluster analysis identified a subgroup characterized by relatively elevated striatal A\u03b2 deposition, particularly A\u03b2Np3E. Collectively, these findings indicate that the severity of A\u03b2 deposition is not directly associated with suicide. However, early involvement of the NAc may contribute to depressive states, and region\u2010specific A\u03b2 species\u2014particularly A\u03b242, A\u03b243, and A\u03b2Np3E\u2014may be associated with increased cognitive vulnerability in this age group.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70124","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T02:03:38Z","timestamp":1784340218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathological and molecular heterogeneity of amyloid\u2010\u03b2 in unnatural deaths under 70\u2009years: A forensic autopsy\u2013based study"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-8137","authenticated-orcid":false,"given":"Shojiro","family":"Ichimata","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Neurology Toyama University Hospital  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-5242","authenticated-orcid":false,"given":"Shigeo","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Neuropathology (Brain Bank for Aging Research) Tokyo Metropolitan Institute for Geriatrics and Gerontology  Tokyo Japan"},{"name":"Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development Osaka University  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.14283\/jpad.2021.15","article-title":"The epidemiology of Alzheimer's disease modifiable risk factors and prevention","volume":"8","author":"Zhang XX","year":"2021","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/diseases12060110","article-title":"Early\u2010 and late\u2010onset Alzheimer's disease: two sides of the same coin?","volume":"12","author":"Valdez\u2010Gaxiola CA","year":"2024","journal-title":"Diseases"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1038\/s41380-022-01531-9","article-title":"Dissecting the 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