{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T02:46:59Z","timestamp":1777344419114,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kamprad Research Foundation","award":["#20200063"],"award-info":[{"award-number":["#20200063"]}]},{"name":"Kamprad Research Foundation","award":["#8024247192"],"award-info":[{"award-number":["#8024247192"]}]},{"name":"Kamprad Research Foundation","award":["#202104517"],"award-info":[{"award-number":["#202104517"]}]},{"name":"Kamprad Research Foundation","award":["#2023-907"],"award-info":[{"award-number":["#2023-907"]}]},{"name":"Ulla-Carin Lindquist Foundation for ALS Research","award":["#20200063"],"award-info":[{"award-number":["#20200063"]}]},{"name":"Ulla-Carin Lindquist Foundation for ALS Research","award":["#8024247192"],"award-info":[{"award-number":["#8024247192"]}]},{"name":"Ulla-Carin Lindquist Foundation for ALS Research","award":["#202104517"],"award-info":[{"award-number":["#202104517"]}]},{"name":"Ulla-Carin Lindquist Foundation for ALS Research","award":["#2023-907"],"award-info":[{"award-number":["#2023-907"]}]},{"name":"Magnus Bergvall foundation","award":["#20200063"],"award-info":[{"award-number":["#20200063"]}]},{"name":"Magnus Bergvall foundation","award":["#8024247192"],"award-info":[{"award-number":["#8024247192"]}]},{"name":"Magnus Bergvall foundation","award":["#202104517"],"award-info":[{"award-number":["#202104517"]}]},{"name":"Magnus Bergvall foundation","award":["#2023-907"],"award-info":[{"award-number":["#2023-907"]}]},{"name":"Magnus Bergvall foundation","award":["#20200063"],"award-info":[{"award-number":["#20200063"]}]},{"name":"Magnus Bergvall foundation","award":["#8024247192"],"award-info":[{"award-number":["#8024247192"]}]},{"name":"Magnus Bergvall foundation","award":["#202104517"],"award-info":[{"award-number":["#202104517"]}]},{"name":"Magnus Bergvall foundation","award":["#2023-907"],"award-info":[{"award-number":["#2023-907"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant trait. Over 100 point mutations have been identified, with the Val30Met substitution being the most common. Yet, the mechanism of pathogenesis and the overall origin of hATTR remain unclear. Here, we argue that hATTR could be related to harmful metal exposure. hATTR incidence is unevenly distributed globally, and the three largest defined clusters exist in Japan, Portugal, and Sweden. All three disease regions are also ancient mining districts with associated metal contamination of the local environment. There are two main mechanisms for how harmful metals, after uptake into tissues and body fluids, could induce hATTR. First, the metals could directly influence the expression, function, and\/or aggregation of the proteins involved in hATTR pathology. Such metal\u2013protein interactions might constitute molecular targets for anti-hATTR drug design. Second, metal exposure could induce hATTR -associated genetic mutations, which may have happened several generations ago. These two mechanisms can occur in parallel. In conclusion, the possibility that hATTR could be related to metal exposure in geochemically defined regions deserves further attention.<\/jats:p>","DOI":"10.3390\/biom14060652","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:06:01Z","timestamp":1717409161000},"page":"652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-9687","authenticated-orcid":false,"given":"Per M.","family":"Roos","sequence":"first","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden"},{"name":"Department of Physiology, St. G\u00f6ran Hospital University Unit, 11281 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-1838","authenticated-orcid":false,"given":"Sebastian K. T. S.","family":"W\u00e4rml\u00e4nder","sequence":"additional","affiliation":[{"name":"Chemistry Section, Stockholm University, 10691 Stockholm, Sweden"},{"name":"CellPept Sweden AB, Kvarngatan 10B, 11847 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/S1474-4422(11)70246-0","article-title":"Familial amyloid polyneuropathy","volume":"10","author":"Said","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.5935\/1518-0557.20170025","article-title":"Corino de Andrade disease: Mechanisms and impact on reproduction","volume":"21","author":"Lopes","year":"2017","journal-title":"JBRA Assist. 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