Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen
{"title":"利用具有遗传信息的成年男性双胞胎样本，测试淀粉样变性对总 Tau 的因果影响。","authors":"Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen","doi":"10.1101/2024.07.23.602498","DOIUrl":null,"url":null,"abstract":"INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"40 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.\",\"authors\":\"Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen\",\"doi\":\"10.1101/2024.07.23.602498\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.\",\"PeriodicalId\":501471,\"journal\":{\"name\":\"bioRxiv - Pathology\",\"volume\":\"40 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv - Pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.07.23.602498\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Pathology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.07.23.602498","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.
INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.
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