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

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.

doi:10.1016/j.nicl.2019.101848

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

Journal Article · Thu May 02 00:00:00 EDT 2019 · NeuroImage: Clinical

DOI:https://doi.org/10.1016/j.nicl.2019.101848· OSTI ID:1604668

^[1]; Iaccarino, Leonardo ^[2]; Schonhaut, Daniel R. ^[3]; Brown, Jesse A. ^[2]; La Joie, Renaud ^[3]; O'Neil, James P. ^[4]; Janabi, Mustafa ^[4]; Baker, Suzanne L. ^[4]; Kramer, Joel H. ^[2]; Gorno-Tempini, Maria-Luisa ^[2]; Miller, Bruce L. ^[2]; Rosen, Howard J. ^[2]; Seeley, William W. ^[2]; Jagust, William J. ^[5]; Rabinovici, Gil D. ^[3]

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)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes on Aging; Marie Curie FP7 International Outgoing Fellowship; John Douglas French Alzheimer's Foundation; State of California

Grant/Contract Number:: AC02-05CH11231; R01-AG045611; R01-AG034570; P50-AG023501; 04-33516

OSTI ID:: 1604668

Journal Information:: NeuroImage: Clinical, Vol. 23, Issue C; ISSN 2213-1582

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 41 works

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Three-year changes of cortical 18F-FDG in amnestic vs. non-amnestic sporadic early-onset Alzheimer’s disease Vanhoutte, Matthieu; Semah, Franck; Leclerc, Xavier European Journal of Nuclear Medicine and Molecular Imaging, Vol. 47, Issue 2 https://doi.org/10.1007/s00259-019-04519-w	journal	October 2019
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Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis Pagani, M.; Chio, A.; Valentini, M. C. Neurology, Vol. 83, Issue 12 https://doi.org/10.1212/WNL.0000000000000792	journal	August 2014

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60 APPLIED LIFE SCIENCES
Alzheimer's disease
flortaucipir
functional connectivity
PET
tau
amyloid

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

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