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 »
- Authors:
-
[1];
- Univ. of California, San Francisco, CA (United States); Univ. of California, Berkelely, CA (United States); VU Univ. Medical Center, Amsterdam (Netherlands)
- Univ. of California, San Francisco, CA (United States)
- Univ. of California, San Francisco, CA (United States); Univ. of California, Berkelely, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Univ. of California, Berkelely, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (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. 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. 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 = {Thu May 02 00:00:00 EDT 2019},
month = {Thu May 02 00:00:00 EDT 2019}
}
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