Abstract
Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer’s disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer’s disease, autosomal dominant Alzheimer’s disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages. Finally, our results suggest tau imaging measures total tau burden in Alzheimer’s disease, composed predominantly of tangle and thread pathology.
| Original language | English |
|---|---|
| Pages (from-to) | 2475-2480 |
| Number of pages | 6 |
| Journal | Annals of Clinical and Translational Neurology |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2020 |
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In: Annals of Clinical and Translational Neurology, Vol. 7, No. 12, 12.2020, p. 2475-2480.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Ante- and postmortem tau in autosomal dominant and late-onset Alzheimer’s disease
AU - for the Dominantly Inherited Alzheimer Network (DIAN) and for the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU)
AU - Chen, Charles D.
AU - Holden, Timothy R.
AU - Gordon, Brian A.
AU - Franklin, Erin E.
AU - Li, Yan
AU - Coble, Dean W.
AU - Luo, Hongbo
AU - Bateman, Randall J.
AU - Ances, Beau M.
AU - Perrin, Richard J.
AU - Benzinger, Tammie L.S.
AU - Cairns, Nigel J.
AU - Morris, John C.
N1 - Funding Information: R.J.B. is the principal investigator of the DIAN‐TU, which is supported in part by the DIAN‐TU Pharma Consortium. Eli Lilly and Company and Hoffman‐LaRoche, two members of the DIAN‐TU Pharma Consortium, provided funding for the DIAN‐TU‐001 trial, the former additionally providing technology transfer and precursor for F‐flortaucipir, the tau PET radioligand used in this study, and the latter additionally providing payment and reimbursement for speaking fees, advisory boards, and travel expenses of R.J.B. Additionally, B.A.G., Y.L., D.W.C., R.J.P., and T.L.S.B. are also members of the DIAN‐TU, and T.L.S.B. additionally participates as a site investigator in clinical trials sponsored by Eli Lilly and Company. 18 Funding Information: This study was supported by the Knight Alzheimer Disease Research Center (Knight ADRC, NIH grants P50AG005681, P01AG026276, P01AG03991), the Dominantly Inherited Alzheimer Network (DIAN, NIH grants U19AG032438, R01AG052550‐01A1), the DIAN Trials Unit (DIAN‐TU, NIH grants U01AG042791, U01AG042791‐S1, R01AG046179, R01AG53267‐S1, as well as support from the Alzheimer's Association, GHR Foundation, an anonymous organization, the DIAN‐TU Pharma Consortium, Eli Lilly and Company, Roche, Avid Radiopharmaceuticals, CogState and Bracket), and the Neuroimaging Informatics and Analysis Center (P30NS098577). The authors were supported by grants from the NSF (DGE‐1745038) and NIH (K01AG053474, UF1AG032438). Funding Information: Data collection and sharing for this project was supported by the Knight Alzheimer Disease Research Center (Knight ADRC, NIH grants P50AG005681, P01AG026276, P01AG03991), the Dominantly Inherited Alzheimer Network (DIAN, NIH U19AG032438), and the DIAN Trials Unit (DIAN-TU). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. The authors thank the altruism of the participants and their families and contributions of the Knight ADRC and DIAN research and support staff at each of the participating sites for their contributions to this study. For the provision of brain tissue and staining, we acknowledge the Knight ADRC Neuropathology Core and the DIAN Neuropathology Core (NIH P01AG003991). The authors also thank support for tau PET imaging in DIAN (NIH R01AG052550-01A1), as well as the Neuroimaging Informatics and Analysis Center (NIH P30NS098577). C.D.C. thanks the support from the NSF GRFP (DGE-1745038). B.A.G. thanks the support from the NIH (K01AG053474). J.C.M. thanks the support from the NIH (UF1AG032438). The DIAN-TU is supported by the Alzheimer?s Association, GHR Foundation, an anonymous organization, and the DIAN-TU Pharma Consortium (https://dian.wustl.edu/our-research/the-pharma-consortium/). This research for the DIAN-TU-001 Trial has received support from the Alzheimer?s Association, Eli Lilly and Company, Roche, NIH grants U01AG042791, U01AG042791-S1 (FNIH and Accelerating Medicines Partnership), R01AG046179, R01AG53267-S1, Avid Radiopharmaceuticals, GHR Foundation, and an anonymous organization. In-kind support has been received from CogState and Bracket. The authors thank the altruism of the participants and their families and contributions of the DIAN and DIAN-TU research and support staff at each of the participating sites (https://dian.wustl.edu/wp-content/uploads/2019/04/DIAN-TU-Publications_Acknowledgement_V26.pdf) for their contributions to this study. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided technology transfer and precursor for 18F-flortaucipir. Funding Information: Data collection and sharing for this project was supported by the Knight Alzheimer Disease Research Center (Knight ADRC, NIH grants P50AG005681, P01AG026276, P01AG03991), the Dominantly Inherited Alzheimer Network (DIAN, NIH U19AG032438), and the DIAN Trials Unit (DIAN‐TU). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. The authors thank the altruism of the participants and their families and contributions of the Knight ADRC and DIAN research and support staff at each of the participating sites for their contributions to this study. For the provision of brain tissue and staining, we acknowledge the Knight ADRC Neuropathology Core and the DIAN Neuropathology Core (NIH P01AG003991). The authors also thank support for tau PET imaging in DIAN (NIH R01AG052550‐01A1), as well as the Neuroimaging Informatics and Analysis Center (NIH P30NS098577). C.D.C. thanks the support from the NSF GRFP (DGE‐1745038). B.A.G. thanks the support from the NIH (K01AG053474). J.C.M. thanks the support from the NIH (UF1AG032438). The DIAN‐TU is supported by the Alzheimer’s Association, GHR Foundation, an anonymous organization, and the DIAN‐TU Pharma Consortium ( https://dian.wustl.edu/our‐research/the‐pharma‐consortium/ ). This research for the DIAN‐TU‐001 Trial has received support from the Alzheimer’s Association, Eli Lilly and Company, Roche, NIH grants U01AG042791, U01AG042791‐S1 (FNIH and Accelerating Medicines Partnership), R01AG046179, R01AG53267‐S1, Avid Radiopharmaceuticals, GHR Foundation, and an anonymous organization. In‐kind support has been received from CogState and Bracket. The authors thank the altruism of the participants and their families and contributions of the DIAN and DIAN‐TU research and support staff at each of the participating sites ( https://dian.wustl.edu/wp‐content/uploads/2019/04/DIAN‐TU‐Publications_Acknowledgement_V26.pdf ) for their contributions to this study. Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided technology transfer and precursor for F‐flortaucipir. 18 Publisher Copyright: © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
PY - 2020/12
Y1 - 2020/12
N2 - Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer’s disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer’s disease, autosomal dominant Alzheimer’s disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages. Finally, our results suggest tau imaging measures total tau burden in Alzheimer’s disease, composed predominantly of tangle and thread pathology.
AB - Antemortem tau positron emission tomography imaging suggests elevated tau pathology in autosomal dominant versus late-onset Alzheimer’s disease at equivalent clinical stages, but does not implicate the specific tau pathologies responsible. Here we made stereological measurements of tau neurofibrillary tangles, neuritic plaques, and neuropil threads and found compared to late-onset Alzheimer’s disease, autosomal dominant Alzheimer’s disease showed even greater tangle and thread burdens. Regional tau burden resembled that observed in tau imaging of a separate cohort at earlier clinical stages. Finally, our results suggest tau imaging measures total tau burden in Alzheimer’s disease, composed predominantly of tangle and thread pathology.
UR - http://www.scopus.com/inward/record.url?scp=85096659069&partnerID=8YFLogxK
U2 - 10.1002/acn3.51237
DO - 10.1002/acn3.51237
M3 - Article
C2 - 33150749
AN - SCOPUS:85096659069
SN - 2328-9503
VL - 7
SP - 2475
EP - 2480
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 12
ER -