{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:06:58Z","timestamp":1777396018716,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"<jats:p>Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) is a disease in which the clinical presentation mimics that of Alzheimer\u2019s disease. TDP-43 proteinopathy associated with LATE has been identified in more than 20% of autopsies of community-dwelling adults over the age of 80. It is believed to contribute significantly toward tau-negative dementia. Heavy metals such as lead has also been linked to TDP-43 proteinopathy. In particular, lead triggers TDP-43 accumulation and disrupts TDP-43 homeostasis. However, the specific relationship between LATE and lead remains unknown. Before leaded gasoline was phased out during the 1970s and 1980s, average blood lead levels were 15 times what they are today. Thus, each successive birth cohort entering old age has had less cumulative lifeime exposure to lead. Lifetime exposure can be tracked in the tibia bone, where the half-life of lead is many decades. We hypothesize that lead plays a role in the development of LATE. There are two ways to explore the validity of this hypothesis. Generational differences in lead exposure should result in a steady decline in the prevalence of LATE among older adults. We propose the use of tibia bone lead levels be examined in conjunction with brain autopsies from different birth cohorts to examine the link between lead exposure and LATE prevalence, holding age constant. Furthermore, individuals with genetic polymorphisms that confer a greater lead absorption phenotype should display a higher degree of TDP-43 accumulation in autopsies. The results of such studies could provide insight into gene by environment interactions relevant to the development of LATE.<\/jats:p>","DOI":"10.3233\/jad-190943","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T04:30:23Z","timestamp":1575520223000},"page":"455-459","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Could Lifetime Lead Exposure Play a Role in Limbic-predominant Age-related TDP-43 Encephalopathy (LATE)?"],"prefix":"10.1177","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-6216","authenticated-orcid":false,"given":"Esme","family":"Fuller-Thomson","sequence":"first","affiliation":[{"name":"Institute for Life Course & Aging, Factor-Inwentash Faculty of Social Work, Toronto, ON, Canada"},{"name":"Faculty of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-4254","authenticated-orcid":false,"given":"ZhiDi","family":"Deng","sequence":"additional","affiliation":[{"name":"Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfy267"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13625"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz224"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31817713b5"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0261-2"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0000000000000266"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq063"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.2174\/1874205X00802010051"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1983.00350020038008"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh333"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000239836.26142.c5"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.2174\/156720512800617991"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9786"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32399-6"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1408322"},{"key":"ref017","volume-title":"Seasonality of Moves and the Duration and Tenure of Residence, 2004","author":"Marlay MC","year":"2010"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03520040046039"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.05.042"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6525e1"},{"key":"ref021","unstructured":"ATSDR \u2013 Environmental Medicine & Environmental Health Education \u2013 CSEM (2017) Lead Toxicity: What is the Biological Fate of Lead in the Body? https:\/\/www.atsdr.cdc.gov\/csem\/csem.asp?csem=34&po=9."},{"key":"ref022","volume-title":"Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations","author":"National Research Council","year":"1993"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.8.1171"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1136\/oem.57.8.535"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(78)90253-6"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0b013e3181aa0106"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1097\/JOM.0b013e31822589a9"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2018.2163"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2011.087"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.4172\/2161-0525.1000118"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.11.008"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.11233"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2015.11.001"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00121"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.07.034"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.11.118"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-7125(16)30354-6"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190943","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-190943","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190943","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:07:22Z","timestamp":1777370842000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-190943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,3]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1,21]]}},"alternative-id":["10.3233\/JAD-190943"],"URL":"https:\/\/doi.org\/10.3233\/jad-190943","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,3]]}}}