@article{c86d6af1b4d74425a5bc3004772afd72,
title = "Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study",
abstract = "Background: Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-beta (A beta) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.Methods: Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of A beta (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.Results: Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with A beta accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (similar to 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.Conclusions: Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between A beta burden and neocortical tau accumulation in ADAD.",
keywords = "alzheimer's, amyloid, autosomal-dominant, imaging, longitudinal, tau, Longitudinal, Imaging, Autosomal-Dominant, Tau, Amyloid, Alzheimer's",
author = "J.S. Sanchez and B.J. Hanseeuw and F. Lopera and R.A. Sperling and A. Baena and Y. Bocanegra and D. Aguillon and E. Guzman-Velez and E. Pardilla-Delgado and L. Ramirez-Gomez and C. Vila-Castelar and J.E. Martinez and J.T. Fox-Fuller and C. Ramos and M. Ochoa-Escudero and S. Alvarez and H.I.L. Jacobs and A.P. Schultz and J.R. Gatchel and J.A. Becker and S.R. Katz and D.V. Mayblyum and J.C. Price and E.M. Reiman and K.A. Johnson and Y.T. Quiroz",
note = "Funding Information: Dr. Quiroz was supported by grants from the NIH Office of the Director (DP5OD019833), the National Institute on Aging (R01AG054671), the Alzheimer{\textquoteright}s Association, and Massachusetts General Hospital ECOR (1200-228010 and 1200-228767). Dr. Lopera was supported by an Anonymous Foundation, and the Administrative Department of Science, Technology and Innovation (Colciencias Colombia; 111565741185). Dr. Jacobs receives funding from the NIH-NIA R01AG062559. Mr. Fox-Fuller reports support from the NIH-NIA National Research Service Award (1F31AG062158-01A1). Dr. Gatchel is supported by NIH/NIA (K23 AG058805-01), Alzheimer{\textquoteright}s Association Clinical Fellowship (AACF_16-440965), and the Massachusetts General Hospital Rappaport Fellowship. Dr. Reiman reports grants from National Institute on Aging (R01 AG031581, P30 AG19610), Banner Alzheimer{\textquoteright}s Foundation and the NOMIS Foundation during the conduct of the study. Dr. Sperling receives research support for NIH grants P01AG036694, P50AG005134, 2009-2020, and U19 AG10483, as well as from Eli Lilly (clinical trial) and the Alzheimer{\textquoteright}s Association. Dr. Johnson has received support from a joint NIH-Lilly-sponsored clinical trial (A4 Study - U19AG10483) and received research support from NIH grants R01 AG027435, P50 AG00513421, AG036694, R01 AG046396, R13 AG042201174210, U19AG10483, and U01AG024904, as well as the Alzheimer Association and Marr Foundation. Funding Information: Dr. Reiman reports receiving personal fees as a Scientific Advisor to Roche Diagnostics (travel expenses only), MagQ, Avid Radiopharmaceuticals, and is a share-holding co-founder of ALZPath, outside the submitted work. In addition, he is the inventor of a patent issued to Banner Health, which involves the use of biomarker endpoints in at-risk persons to accelerate the evaluation of Alzheimer{\textquoteright}s disease prevention therapies and is outside the submitted work. Drs. Reiman and Lopera are principal investigators of the Alzheimer{\textquoteright}s Prevention Initiative (API) Autosomal Dominant AD Trial, which is supported by NIA, philanthropy, Genentech, and Roche. Dr. Sperling is a site principal investigator or coinvestigator for Avid, Bristol-Myers Squibb, Pfizer, and Janssen Alzheimer Immunotherapy clinical trials. She receives travel funding and honoraria from AC Immune, Janssen, and Roche. She consults for Biogen, Roche, AC Immune, Eisai, Takeda, Neurocentria, and Janssen. Spouse consults for Novartis, AC Immune, and Janssen. Dr. Johnson has provided consulting services for Novartis, Biogen, and Eli Lilly. All other co-authors have no competing interests or disclosures relevant to the manuscript. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jan,
day = "15",
doi = "10.1186/s13195-020-00765-5",
language = "English",
volume = "13",
journal = "Alzheimer's Research & Therapy",
issn = "1758-9193",
publisher = "BioMed Central Ltd",
number = "1",
}