Four distinct trajectories of tau deposition identified in Alzheimer’s disease

Authors

Jacob W. Vogel, Institut-Hôpital Neurologique de Montréal
Alexandra L. Young, King's College London
Neil P. Oxtoby, University College London
Ruben Smith, Lunds Universitet
Rik Ossenkoppele, Lunds Universitet
Olof T. Strandberg, Lunds Universitet
Renaud La Joie, University of California, San Francisco
Leon M. Aksman, University College London
Michel J. Grothe, Göteborgs Universitet
Yasser Iturria-Medina, Institut-Hôpital Neurologique de Montréal
Michael Weiner, University of California, San Francisco
Paul Aisen, University of California, San Diego
Ronald Petersen, Mayo Clinic
Clifford R. Jack, Mayo Clinic
William Jagust, University of California, Berkeley
John Q. Trojanowki, University of Pennsylvania
Arthur W. Toga, University of Southern California
Laurel Beckett, University of California, Davis
Robert C. Green, Harvard Medical School
Andrew J. Saykin, Indiana University Bloomington
John Morris, Washington University in St. Louis
Leslie M. Shaw, University of Pennsylvania
Enchi Liu, Janssen Alzheimer Immunotherapy
Tom Montine, University of Washington
Ronald G. Thomas, University of California, San Diego
Michael Donohue, University of California, San Diego
Sarah Walter, University of California, San Diego
Devon Gessert, University of California, San Diego
Tamie Sather, University of California, San Diego
Gus Jiminez, University of California, San Diego
Danielle Harvey, University of California, Davis
Matthew Bernstein, Mayo Clinic

Document Type

Article

Publication Date

5-1-2021

Journal

Nature Medicine

Volume

27

Issue

5

First Page

871

Last Page

881

URL with Digital Object Identifier

10.1038/s41591-021-01309-6

Abstract

Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging.