Ethics approval and consent to participate
The TRIAD study was approved by the Montreal Neurological Institute PET Working Committee and the Douglas Mental Health University Institute Research Ethics Board. Written informed consent was obtained from all participants.
Consent for publication
Not applicable.
Data availability
Data from the TRIAD cohort that support the findings of this study are available from the corresponding author upon reasonable request. All requests for raw and analyzed data and materials will be promptly reviewed by McGill University to verify if the request is subject to any intellectual property or confidentiality obligations. Anonymized data will be shared upon request from a qualified academic investigator for the purpose of replicating the procedures and results presented in this article. Any data and materials that can be shared will be released via a material transfer agreement. Data are not publicly available due to information that could compromise the privacy of research participants.
Competing interests
The authors have no conflicts of interest to report related to this work. Outside the work presented in this paper, PRN provides consultancy services for Roche, Cerveau Radiopharmaceuticals, Lilly, Eisai, Pfizer, and Novo Nordisk. He also serves as a clinical trials investigator for Biogen, Novo Nordisk, and Biogen. HZ has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant and on advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Julius Clinical, Lilly, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for Biogen, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. JT has received consulting fees from the Neurotorium educational platform. SG is a member of the scientific advisory boards of Alzheon, AmyriAD, Eisai Canada, Enigma USA, Lilly Canada, Medesis, Okutsa Canada, Roche Canada, and TauRx. He is a member of the editorial board of JPAD and of the Neurotorium. He has given lectures under the auspices of Biogen Canada and Lundbeck Korea.
Funding
This work was supported by the Canadian Institutes of Health Research (CIHR) [MOP-11-51-31; RFN 152985, 159815, 162303], Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1), Weston Brain Institute, the Alzheimer’s Association [NIRG-12-92090, NIRP-12-259245], Brain Canada Foundation (CFI Project 34874; 33397), the Fonds de Recherche du Québec – Santé (FRQS; Chercheur Boursier, 2020-VICO-279314).
Unrelated to the work presented in this paper, YTW received the FRQS doctoral award. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). KB is supported by the Swedish Research Council (#2017-00915 and #2022-00732), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721 and #AF-968270), Hjärnfonden, Sweden (#FO2017-0243 and #ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), and the Alzheimer’s Association 2022-2025 Grant (SG-23-1038904 QC). MSW is supported by the Joachim-Herz Foundation. ALB is supported by the CAPES Foundation and the Alzheimer’s Association Grant (AARFD-22-974564).
Author contributions
NJA, JN, AB and ALB conducted the biomarker measurements. YW and ALB analyzed and interpreted the data. SS, MSW, TAP, CT, NR, JT, FL, MC, SG, PRN, and ALB contributed to participants’ data and samples as well as with technical/scientific support. YW, NJA, HZ, KB, PRN, and ALB designed the study and wrote the manuscript. All authors critically reviewed and approved the final manuscript.
Acknowledgements
We would like to express our gratitude to our participant volunteers and their families for their participation in this study. We thank the staff, the research nurses, the psychometrist and the neurologist at the McGill Centre for Studies in Aging for their contribution. We thank the radiographers and technicians at the McConnell Brain Imaging Centre and The Neuro (Montreal Neurological Institute-Hospital) for their role in imaging data acquisition. We also thank the scientists at the University of Gothenburg for their role in analyzing the CSF data.