Distinct tau PET dynamics in early versus late age-of-onset Alzheimer’s disease
Abstract
Early-onset Alzheimer's disease (EOAD) and Late-onset AD (LOAD) differ in clinical presentations and rates of progression. We aimed to compare baseline and longitudinal tau PET burden, and their relationship with clinical variables in amyloid-PET positive, cognitively impaired participants from the Longitudinal Early-Onset Alzheimer's Disease Study (EOAD; n=390) and Alzheimer's Disease Neuroimaging Initiative (LOAD; n=211). Patients with EOAD showed higher baseline tau PET retention, broader neuroanatomical involvement and faster accumulation rates over time compared to LOAD, after adjusting for amyloid load and clinical stage. Tau PET showed stronger correlations with baseline amyloid burden and clinical measures of global cognition and function in EOAD than LOAD. We conclude that earlier age of onset in AD is linked to a more aggressive tauopathy, which in turn is a primary driver of clinical decline. These findings suggest that optimal therapeutic targets and strategies may differ between EOAD and LOAD.
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Authors: Konstantinos Chiotis, Ganna Blazhenets, David N. Soleimani‐Meigooni, Paul S. S Aisen, Alinda N. Amuiri, Alireza Atri, Laurel A. Beckett, Michael J. Brickhouse, David Glenn Clark, Jeffrey L. Dage, Gregory Scott Day, Ranjan Duara, Ani Eloyan, Tatiana Foroud, Neill R. Graff‐Radford, Ian M. Grant, Dustin B. Hammers, Lawrence S. Honig, Erik C. B. Johnson, David Thomas Jones, Kala Kirby, Robert A. Koeppe, Joel H. Kramer, Walter A. Kukull, Julien Lagarde, Antoine Leuzy, Piyush Maiti, Joseph C. Masdeu, Mario F. Mendez, Erik S. Musiek, Kelly Nicole Holohan Nudelman, Chiadi U. Onyike, Meghan Riddle, Salma Rocha, Emily Joy Rogalski, Stephen Salloway, Daniel R. Schonhaut, Sharon J. Sha, Ranjani P. Shankar, Alexander Taurone, Maryanne Thangarajah, Arthur W. Toga, Alexandra Touroutoglou, Raymond Scott Turner, Prashanthi Vemuri, Thomas S. Wingo, David A. Wolk, Kyle B. Womack, Jiaxiuxiu Zhang, María C. Carrillo, Bradford Clark Dickerson, Liana G. Apostolova, Renaud La Joie, Gil Dan Rabinovici
Institutions: University of Pennsylvania, University of California, Los Angeles, Georgetown University, University of Washington, Northwestern University, Karolinska Institutet, Columbia University, Johns Hopkins University, Brown University, University of California, San Francisco, University of Michigan, Emory University, Washington University in St. Louis, Karolinska University Hospital, Indiana University School of Medicine, Stanford University, Columbia University Irving Medical Center, Massachusetts General Hospital, University of California, Davis, Keck Hospital of USC, Mayo Clinic, Weill Cornell Medicine, Michigan Medicine, Mayo Clinic in Florida, University of San Francisco, Banner Sun Health Research Institute, Southern States University, Houston Methodist, Indiana University Indianapolis, Mount Sinai Medical Center, Alzheimer's Association