1. Neuroscience
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Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

  1. Jenna N Adams  Is a corresponding author
  2. Anne Maass
  3. Theresa M Harrison
  4. Suzanne L Baker
  5. William J Jagust
  1. University of California, Berkeley, United States
  2. Lawrence Berkeley National Laboratory, United States
Research Article
  • Cited 28
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Cite this article as: eLife 2019;8:e49132 doi: 10.7554/eLife.49132

Abstract

Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex (alEC) in the aging brain. The transition to Alzheimer's disease (AD) is hypothesized to involve amyloid-b (Ab) facilitated tau spread through neural connections. We contrasted functional connectivity (FC) of alEC and posteromedial EC (pmEC), subregions of EC that differ in functional specialization and cortical connectivity, with the hypothesis that alEC-connected cortex would show greater tau deposition than pmEC-connected cortex. We used resting state fMRI to measure FC, and PET to measure tau and Aβ in cognitively normal older adults. Tau preferentially deposited in alEC-connected cortex compared to pmEC-connected or non-connected cortex, and stronger connectivity was associated with increased tau deposition. FC-tau relationships were present regardless of Aβ, though strengthened with Aβ. These results provide an explanation for the anatomic specificity of neocortical tau deposition in the aging brain and reveal relationships between normal aging and the evolution of AD.

Data availability

Data analyzed during this study are available as supporting files. Source data files have been provided for Table 1, Figure 2, Figure 2-figure supplement 1, Figure 3, Figure 3-figure supplement 1, and Supplementary File 2.

Article and author information

Author details

  1. Jenna N Adams

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    For correspondence
    jnadams@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6702-3851
  2. Anne Maass

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Theresa M Harrison

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Suzanne L Baker

    Lawrence Berkeley National Laboratory, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. William J Jagust

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4458-113X

Funding

National Institutes of Health (R01-AG034570)

  • William J Jagust

National Institutes of Health (F32-AG057107)

  • Theresa M Harrison

Helmholtz Postdoc Program (PD-306)

  • Anne Maass

Tau Consortium

  • William J Jagust

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All participants provided written informed consent. This study was approved by the Lawrence Berkeley National Laboratory institutional review board (protocol # 073H026).

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: June 7, 2019
  2. Accepted: August 31, 2019
  3. Accepted Manuscript published: September 2, 2019 (version 1)
  4. Version of Record published: September 27, 2019 (version 2)

Copyright

© 2019, Adams et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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