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Title: Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

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-β (Aβ) 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, although 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.

Authors:
ORCiD logo [1];  [2]; ORCiD logo [1]; ORCiD logo [3]; ORCiD logo [4]
  1. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
  2. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; German Center for Neurodegenerative Disease, Magdeburg (Germany)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH); Helmholtz-Gemeinschaft; Tau Consortium
OSTI Identifier:
1572050
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Adams, Jenna N., Maass, Anne, Harrison, Theresa M., Baker, Suzanne L., and Jagust, William J. Cortical tau deposition follows patterns of entorhinal functional connectivity in aging. United States: N. p., 2019. Web. doi:10.7554/eLife.49132.
Adams, Jenna N., Maass, Anne, Harrison, Theresa M., Baker, Suzanne L., & Jagust, William J. Cortical tau deposition follows patterns of entorhinal functional connectivity in aging. United States. doi:10.7554/eLife.49132.
Adams, Jenna N., Maass, Anne, Harrison, Theresa M., Baker, Suzanne L., and Jagust, William J. Mon . "Cortical tau deposition follows patterns of entorhinal functional connectivity in aging". United States. doi:10.7554/eLife.49132. https://www.osti.gov/servlets/purl/1572050.
@article{osti_1572050,
title = {Cortical tau deposition follows patterns of entorhinal functional connectivity in aging},
author = {Adams, Jenna N. and Maass, Anne and Harrison, Theresa M. and Baker, Suzanne L. and Jagust, William J.},
abstractNote = {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-β (Aβ) 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, although 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.},
doi = {10.7554/eLife.49132},
journal = {eLife},
number = ,
volume = 8,
place = {United States},
year = {2019},
month = {9}
}

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