Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease

Jacob W. Vogel, Institut-Hôpital Neurologique de Montréal
Yasser Iturria-Medina, Institut-Hôpital Neurologique de Montréal
Olof T. Strandberg, Lunds Universitet
Ruben Smith, Lunds Universitet
Elizabeth Levitis, Institut-Hôpital Neurologique de Montréal
Alan C. Evans, Institut-Hôpital Neurologique de Montréal
Oskar Hansson, Lunds Universitet
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
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
Nick Fox, University of London
Paul Thompson, Keck School of Medicine of USC
Norbert Schuff, University of California, San Francisco
Charles DeCArli, University of California, Davis

Document Type

Article

Publication Date

12-1-2020

Abstract

Tau is a hallmark pathology of Alzheimer’s disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer’s disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.

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