Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins
The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilam...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Aging Brain |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589958925000052 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849694597856362496 |
|---|---|
| author | Nathan A. Gillespie Michael C. Neale Matthew S. Panizzon Ruth E. McKenzie Xin M. Tu Hong Xian Chandra A. Reynolds Michael J. Lyons Robert A. Rissman Jeremy A. Elman Carol Franz William S. Kremen |
| author_facet | Nathan A. Gillespie Michael C. Neale Matthew S. Panizzon Ruth E. McKenzie Xin M. Tu Hong Xian Chandra A. Reynolds Michael J. Lyons Robert A. Rissman Jeremy A. Elman Carol Franz William S. Kremen |
| author_sort | Nathan A. Gillespie |
| collection | DOAJ |
| description | The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau. No clear evidence that Aβ40 or Aβ42 directly causes t-Tau was observed. Instead, the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL. Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau, though our use of total rather than phosphorylated tau was a limitation. In contrast, Aβ biomarkers appeared to causally impact NFL in cognitively unimpaired men in their late 60 s. |
| format | Article |
| id | doaj-art-2d98f8f4b1c34effb60d9e04d0546939 |
| institution | DOAJ |
| issn | 2589-9589 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Aging Brain |
| spelling | doaj-art-2d98f8f4b1c34effb60d9e04d05469392025-08-20T03:20:01ZengElsevierAging Brain2589-95892025-01-01710013910.1016/j.nbas.2025.100139Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twinsNathan A. Gillespie0Michael C. Neale1Matthew S. Panizzon2Ruth E. McKenzie3Xin M. Tu4Hong Xian5Chandra A. Reynolds6Michael J. Lyons7Robert A. Rissman8Jeremy A. Elman9Carol Franz10William S. Kremen11Virginia Institute for Psychiatric and Behaviour Genetics, Department of Psychiatry, Virginia Commonwealth University, Box 980126, Richmond, VA 23298-0126, USA; QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia; Corresponding author at: Virginia Institute for Psychiatric and Behavioral Genetics of VCU, Box 980126, Richmond, VA 23298-0126, United States.Virginia Institute for Psychiatric and Behaviour Genetics, Department of Psychiatry, Virginia Commonwealth University, Box 980126, Richmond, VA 23298-0126, USADepartment of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USAWinston School of Education and Social Policy at Merrimack College, 315 Turnpike Street, North Andover, MA 01845, USA; Department of Family Medicine and Public Health, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USADepartment of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USA; Department of Epidemiology and Biostatistics, Saint Louis University, 3545 Lafayette Ave, St. Louis, MO 63104, USAResearch Service, VA St. Louis Healthcare System, 1 Jefferson Barracks Drive, St. Louis, MO 63125, USA; Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado, Boulder, 1480 30th Street, Boulder, CO 80309, USADepartment of Psychological and Brain Sciences, Boston University, 64 Cummington Mall, Boston, MA 02215, USASam and Rose Stein Institute for Research on Aging, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USADepartment of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USADepartment of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USADepartment of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USADepartment of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Psychology, Boston University, 64 Cummington Mall, Boston, MA 02215, USAThe amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau. No clear evidence that Aβ40 or Aβ42 directly causes t-Tau was observed. Instead, the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL. Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau, though our use of total rather than phosphorylated tau was a limitation. In contrast, Aβ biomarkers appeared to causally impact NFL in cognitively unimpaired men in their late 60 s.http://www.sciencedirect.com/science/article/pii/S2589958925000052Cascade hypothesisPlasmaAmyloid-betaTauTwinGene |
| spellingShingle | Nathan A. Gillespie Michael C. Neale Matthew S. Panizzon Ruth E. McKenzie Xin M. Tu Hong Xian Chandra A. Reynolds Michael J. Lyons Robert A. Rissman Jeremy A. Elman Carol Franz William S. Kremen Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins Aging Brain Cascade hypothesis Plasma Amyloid-beta Tau Twin Gene |
| title | Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins |
| title_full | Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins |
| title_fullStr | Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins |
| title_full_unstemmed | Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins |
| title_short | Testing the causal impact of plasma amyloid on total Tau using a genetically informative sample of adult male twins |
| title_sort | testing the causal impact of plasma amyloid on total tau using a genetically informative sample of adult male twins |
| topic | Cascade hypothesis Plasma Amyloid-beta Tau Twin Gene |
| url | http://www.sciencedirect.com/science/article/pii/S2589958925000052 |
| work_keys_str_mv | AT nathanagillespie testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT michaelcneale testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT matthewspanizzon testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT ruthemckenzie testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT xinmtu testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT hongxian testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT chandraareynolds testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT michaeljlyons testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT robertarissman testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT jeremyaelman testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT carolfranz testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins AT williamskremen testingthecausalimpactofplasmaamyloidontotaltauusingageneticallyinformativesampleofadultmaletwins |