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

https://doi.org/10.1016/j.nicl.2019.101848Get rights and content
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Highlights

  • Tau covariance patterns in AD resemble functional networks in young adults

  • Hypometabolic patterns spatially resemble tau pathology but are more restricted

  • Topography of Aβ pathology is more diffuse and less network specific

  • Tau pathology may spread through neural networks, driving neurodegeneration

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 through circumscribed brain networks and drives neurodegeneration.

Keywords

Alzheimer's disease
Flortaucipir
Functional connectivity
PET
Tau
Amyloid

Abbreviations

AD
Alzheimer's disease
Amyloid-β
CBS
Corticobasal syndrome
DVR
Distribution volume ratio
EOAD
Early-onset Alzheimer's disease
fMRI
Functional magnetic resonance imaging
GOF
Goodness-of-fit
ICN
Intrinsic connectivity network
LBNL
Lawrence Berkeley National Laboratory
LOAD
Late-onset Alzheimer's disease
lPCC
Left posterior cingulate cortex
lSTG
Left superior temporal gyrus
lvPPA
Logopenic variant primary progressive aphasia
MRI
Magnetic resonance imaging
PCA
Posterior cortical atrophy
PET
Positron emission tomography
rMFG
Right middle frontal gyrus
rMOG
Right middle occipital gyrus
ROI
region-of-interest
SPM
Statistical parametric mapping
SUVR
Standardized uptake value ratio
UCSF
University of California San Francisco

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