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Title: Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain

Abstract

According to the network model of neurodegeneration, the spread of pathogenic proteins occurs selectively along connected brain regions. We tested in vivo whether the distribution of filamentous tau (measured with [18F]flortaucipir-PET), fibrillar amyloid-β ([11C]PIB-PET) and glucose hypometabolism ([18F]FDG-PET) follows the intrinsic functional organization of the healthy brain. We included 63 patients with Alzheimer's disease (AD; 30 male, 63 ± 8 years) who underwent [18F]flortaucipir, [11C]PIB and [18F]FDG PET, and 1000 young adults (427 male, 21 ± 3 years) who underwent task-free fMRI. We selected six predefined disease epicenters as seeds for whole-brain voxelwise covariance analyses to compare correlated patterns of tracer uptake across AD patients against fMRI intrinsic connectivity patterns in young adults. We found a striking convergence between [18F]flortaucipir covariance patterns and intrinsic connectivity maps (range Spearman rho's: 0.32-0.78, p < .001), which corresponded with expected functional networks (range goodness-of-fit: 3.8-8.2). The topography of amyloid-β covariance patterns was more diffuse and less network-specific, while glucose hypometabolic patterns were more spatially restricted than tau but overlapped with functional networks. These findings suggest that the spatial patterns of tau and glucose hypometabolism observed in AD resemble the functional organization of the healthy brain, supporting the notion that tau pathology spreads throughmore » circumscribed brain networks and drives neurodegeneration.« less

Authors:
ORCiD logo [1];  [2];  [3];  [2];  [3];  [4];  [4];  [4];  [2];  [2];  [2];  [2];  [2];  [5];  [3]
  1. Univ. of California, San Francisco, CA (United States); Univ. of California, Berkelely, CA (United States); VU Univ. Medical Center, Amsterdam (Netherlands)
  2. Univ. of California, San Francisco, CA (United States)
  3. Univ. of California, San Francisco, CA (United States); Univ. of California, Berkelely, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  5. Univ. of California, Berkelely, CA (United States); 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 on Aging; Marie Curie FP7 International Outgoing Fellowship; John Douglas French Alzheimer's Foundation; State of California
OSTI Identifier:
1604668
Grant/Contract Number:  
AC02-05CH11231; R01-AG045611; R01-AG034570; P50-AG023501; 04-33516
Resource Type:
Accepted Manuscript
Journal Name:
NeuroImage: Clinical
Additional Journal Information:
Journal Volume: 23; Journal Issue: C; Journal ID: ISSN 2213-1582
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Alzheimer's disease; flortaucipir; functional connectivity; PET; tau; amyloid

Citation Formats

Ossenkoppele, Rik, Iaccarino, Leonardo, Schonhaut, Daniel R., Brown, Jesse A., La Joie, Renaud, O'Neil, James P., Janabi, Mustafa, Baker, Suzanne L., Kramer, Joel H., Gorno-Tempini, Maria-Luisa, Miller, Bruce L., Rosen, Howard J., Seeley, William W., Jagust, William J., and Rabinovici, Gil D. Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain. United States: N. p., 2019. Web. doi:10.1016/j.nicl.2019.101848.
Ossenkoppele, Rik, Iaccarino, Leonardo, Schonhaut, Daniel R., Brown, Jesse A., La Joie, Renaud, O'Neil, James P., Janabi, Mustafa, Baker, Suzanne L., Kramer, Joel H., Gorno-Tempini, Maria-Luisa, Miller, Bruce L., Rosen, Howard J., Seeley, William W., Jagust, William J., & Rabinovici, Gil D. Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain. United States. doi:https://doi.org/10.1016/j.nicl.2019.101848
Ossenkoppele, Rik, Iaccarino, Leonardo, Schonhaut, Daniel R., Brown, Jesse A., La Joie, Renaud, O'Neil, James P., Janabi, Mustafa, Baker, Suzanne L., Kramer, Joel H., Gorno-Tempini, Maria-Luisa, Miller, Bruce L., Rosen, Howard J., Seeley, William W., Jagust, William J., and Rabinovici, Gil D. Thu . "Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain". United States. doi:https://doi.org/10.1016/j.nicl.2019.101848. https://www.osti.gov/servlets/purl/1604668.
@article{osti_1604668,
title = {Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain},
author = {Ossenkoppele, Rik and Iaccarino, Leonardo and Schonhaut, Daniel R. and Brown, Jesse A. and La Joie, Renaud and O'Neil, James P. and Janabi, Mustafa and Baker, Suzanne L. and Kramer, Joel H. and Gorno-Tempini, Maria-Luisa and Miller, Bruce L. and Rosen, Howard J. and Seeley, William W. and Jagust, William J. and Rabinovici, Gil D.},
abstractNote = {According to the network model of neurodegeneration, the spread of pathogenic proteins occurs selectively along connected brain regions. We tested in vivo whether the distribution of filamentous tau (measured with [18F]flortaucipir-PET), fibrillar amyloid-β ([11C]PIB-PET) and glucose hypometabolism ([18F]FDG-PET) follows the intrinsic functional organization of the healthy brain. We included 63 patients with Alzheimer's disease (AD; 30 male, 63 ± 8 years) who underwent [18F]flortaucipir, [11C]PIB and [18F]FDG PET, and 1000 young adults (427 male, 21 ± 3 years) who underwent task-free fMRI. We selected six predefined disease epicenters as seeds for whole-brain voxelwise covariance analyses to compare correlated patterns of tracer uptake across AD patients against fMRI intrinsic connectivity patterns in young adults. We found a striking convergence between [18F]flortaucipir covariance patterns and intrinsic connectivity maps (range Spearman rho's: 0.32-0.78, p < .001), which corresponded with expected functional networks (range goodness-of-fit: 3.8-8.2). The topography of amyloid-β covariance patterns was more diffuse and less network-specific, while glucose hypometabolic patterns were more spatially restricted than tau but overlapped with functional networks. These findings suggest that the spatial patterns of tau and glucose hypometabolism observed in AD resemble the functional organization of the healthy brain, supporting the notion that tau pathology spreads through circumscribed brain networks and drives neurodegeneration.},
doi = {10.1016/j.nicl.2019.101848},
journal = {NeuroImage: Clinical},
number = C,
volume = 23,
place = {United States},
year = {2019},
month = {5}
}

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Works referencing / citing this record:

Three-year changes of cortical 18F-FDG in amnestic vs. non-amnestic sporadic early-onset Alzheimer’s disease
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