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February 3, 2020

Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults

Melissa McSweeney, MSc, Alexa Pichet Binette, MSc, Pierre-François Meyer, PhD, Julie Gonneaud, PhD, Christophe Bedetti, MSc, Hazal Ozlen, BSc, Anne Labonté, BSc, Pedro Rosa-Neto, MD, PhD https://orcid.org/0000-0001-9116-1376, John Breitner, MD, MPH, Judes Poirier, PhD, and Sylvia Villeneuve, PhD for the PREVENT-AD Research GroupAuthors Info & Affiliations
March 17, 2020 issue
94 (11) e1190-e1200
https://doi.org/10.1212/WNL.0000000000008905
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Abstract

Objective

To investigate relationships between flortaucipir (FTP) uptake, age, and established Alzheimer disease (AD) markers in asymptomatic adults at increased risk of AD.

Methods

One-hundred nineteen individuals with a family history of AD (Presymptomatic Evaluation of Experimental or Novel Treatments of Alzheimer’s Disease [PREVENT-AD] cohort, mean age 67 ± 5 years) underwent tau-PET ([18F]FTP), β-amyloid (Aβ)-PET ([18F]NAV4694 [NAV]), and cognitive assessment. Seventy-four participants also had CSF phosphorylated tau and total tau data available. We investigated the association between age and FTP in this relatively young cohort of older adults. We also investigated regional FTP standardized uptake value ratio (SUVR) differences between Aβ-positive and Aβ-negative individuals and regional correlations between FTP and NAV retention. In cortical regions showing consistent associations across analyses, we assessed whether FTP was in addition related to CSF tau and cognitive performance. Lastly, we identified the lowest FTP value at which associations with Aβ-PET, CSF, and cognition were detectable.

Results

Increased age was associated only with amygdala and transverse temporal lobe FTP retention. Aβ-positive individuals had higher FTP SUVR values in several brain regions, further showing correlation with NAV load through the cortex. Increased FTP SUVRs in medial temporal regions were associated with increased CSF tau values and worse cognition. The SUVRs at which associations between entorhinal FTP SUVR and other AD markers were first detected differed by modality, with a detection point of 1.12 for CSF values, 1.2 for Aβ-PET, and 1.4 for cognition.

Conclusions

Relatively low FTP-PET SUVRs are associated with pathologic markers of AD in the preclinical phase of the disease. Adjustment in the tau threshold should be considered, depending on the purpose of the tau classification.

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Information & Authors

Information

Published In

Neurology®
Volume 94 • Number 11 • March 17, 2020
Pages: e1190-e1200
PubMed: 32015176

Copyright

© 2020 American Academy of Neurology.

Publication History

Received: March 22, 2019
Accepted: September 27, 2019
Published online: February 3, 2020
Published in issue: March 17, 2020

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

This study was funded by the Alzheimer Society of Canada and Brain Canada (NIG-17-08), the Quebec Bio-Imaging Network (M.M.), Healthy Brains, Healthy Lives (M.M.), the Alzheimer's Association (NIRG-397028), McGill University (J.B., J.P.), the Fonds de Recherche du Québec–Santé (J.B., J.P.), an unrestricted research grant from Pfizer Canada (J.B., J.P.), the Levesque Foundation (J.P.), the Douglas Hospital Research Centre and Foundation (J.B., J.P.), the Canada Institutes of Health Research (PJT-162091 and PJT-148963), and the Canada Fund for Innovation (S.V.).

Authors

Affiliations & Disclosures

Melissa McSweeney, MSc*
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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1.
NONE
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Alexa Pichet Binette, MSc*
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
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1.
NONE
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Pierre-François Meyer, PhD
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
P.-F.M. is supported by funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative and by the Lazlo & Etelka Kollar fellowship fund for this project.
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
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Julie Gonneaud, PhD
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Christophe Bedetti, MSc
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
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1.
NONE
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Hazal Ozlen, BSc
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Anne Labonté, BSc
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
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1.
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Pedro Rosa-Neto, MD, PhD https://orcid.org/0000-0001-9116-1376
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
(1) Enigma radiopharmaceutical (2) Kalgene
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
associate editor: Frontier in Aging Neurosciences
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Enigma pharmaceuticals (2) Eli-Lilly
Research Support, Government Entities:
1.
(1) FRSQ, 35271, principal applicant, 2014-2018 (2) CIHR, 363444, co-applicant, 2016-2019 (3) CIHR, 366009, co-applicant, 2016-2020 (4) CIHR, 201312CNA-322265-CNA-CFAF-32054, co- investigator, 2014-2019
Research Support, Academic Entities:
1.
(1) Merck, Sharpe & Dohme Corporation/McGill Faculty of Medicine Grant for Translational Research
Research Support, Foundations and Societies:
1.
(1) Weston Brain Institute (2) Alzheimer's Association (3) Brain Canada CQDM
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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John Breitner, MD, MPH
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
(1) Mayo Clinic Studies on Aging, Scientific Advisory Board (NIH-funded program) (2) Data and Safety Monitoring Board, SPRINT-MIND clinical trial (NIA / NHLBI sponsor) (3) Consultant to Cerespir Pharmaceuticals
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Receive occasional honoraria for industry-sponsored talks
Editorial Boards:
1.
Alzheimer's Disease and Associated Disorders, Editorial Board, 2003 - present; PLOS-One, Academics, 2009 - present; Alzheimer's and Dementia, Editorial Board, 2007 - present;
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Research Support (gift) from Pfizer Canada
Research Support, Government Entities:
1.
(1) Fonds de Recherche du Quebec - Sante PI 2012-2015 CIHR 2019-
Research Support, Academic Entities:
1.
(1) Program support from McGill University Faculty of Medicine
Research Support, Foundations and Societies:
1.
(2) Research support from the Douglas Hospital Research Centre and the Douglas Hospital Foundation.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Judes Poirier, PhD
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
1) Fondation Alzheimer (France)
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Alzheimer's Disease, Associate Editor, 2017- 2019
Patents:
1.
NONE
Publishing Royalties:
1.
Young and Centanarian, Trécarré (Canada), 2017 Alzheimer's Disease: The Complete Guide, 2012
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
J.L. Levesque Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Sylvia Villeneuve, PhD
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Canadian Institutes of Health Research, post-doctoral fellowship, 02/12 to 01/15
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
for the PREVENT-AD Research Group
From the Departments of Psychiatry (M.M., A.P.B., P.-F.M., J.G., H.O., P.R.-N., J.B., J.P., S.V.) and Neurology & Neurosurgery (P.R.-N., S.V.), McGill University; Douglas Mental Health University Institute (M.M., A.P.B., J.G., P.-F.M., C.B., H.O., A.L., P.R.-N., J.B., J.P., S.V.); and McConnell Brain Imaging Center, Montreal Neurological Institute (S.V., P.R.-N.), Montreal, Quebec, Canada.
View all articles by this author

Notes

Correspondence Dr. Villeneuve [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
*
These authors contributed equally to this work.
PREVENT-AD Research Group coinvestigators are listed in Appendix 2 at the end of the article.

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