Advanced

Tau pathology distribution in Alzheimer's disease corresponds differentially to cognition-relevant functional brain networks

Hansson, Oskar LU ; Grothe, Michel J.; Strandberg, Tor Olof LU ; Ohlsson, Tomas; Hägerström, Douglas LU ; Jögi, Jonas LU ; Smith, Ruben LU and Schöll, Michael LU (2017) In Frontiers in Neuroscience 11(MAR).
Abstract

Neuropathological studies have shown that the typical neurofibrillary pathology of hyperphosphorylated tau protein in Alzheimer's disease (AD) preferentially affects specific brain regions whereas others remain relatively spared. It has been suggested that the distinct regional distribution profile of tau pathology in AD may be a consequence of the intrinsic network structure of the human brain. The spatially distributed brain regions that are most affected by the spread of tau pathology may hence reflect an interconnected neuronal system. Here, we characterized the brain-wide regional distribution profile of tau pathology in AD using 18F-AV 1451 tau-sensitive positron emission tomography (PET) imaging, and studied this... (More)

Neuropathological studies have shown that the typical neurofibrillary pathology of hyperphosphorylated tau protein in Alzheimer's disease (AD) preferentially affects specific brain regions whereas others remain relatively spared. It has been suggested that the distinct regional distribution profile of tau pathology in AD may be a consequence of the intrinsic network structure of the human brain. The spatially distributed brain regions that are most affected by the spread of tau pathology may hence reflect an interconnected neuronal system. Here, we characterized the brain-wide regional distribution profile of tau pathology in AD using 18F-AV 1451 tau-sensitive positron emission tomography (PET) imaging, and studied this pattern in relation to the functional network organization of the human brain. Specifically, we quantified the spatial correspondence of the regional distribution pattern of PET-evidenced tau pathology in AD with functional brain networks characterized by large-scale resting state functional magnetic resonance imaging (rs-fMRI) data in healthy subjects. Regional distribution patterns of increased PET-evidenced tau pathology in AD compared to controls were characterized in two independent samples of prodromal and manifest AD cases (the Swedish BioFINDER study, n = 44; the ADNI study, n = 35). In the BioFINDER study we found that the typical AD tau pattern involved predominantly inferior, medial, and lateral temporal cortical areas, as well as the precuneus/posterior cingulate, and lateral parts of the parietal and occipital cortex. This pattern overlapped primarily with the dorsal attention, and to some extent with higher visual, limbic and parts of the default-mode network. PET-evidenced tau pathology in the ADNI replication sample, which represented a more prodromal group of AD cases, was less pronounced but showed a highly similar spatial distribution profile, suggesting an earlier-stage snapshot of a consistently progressing regional pattern. In conclusion, the present study indicates that the regional deposition of tau aggregates in AD predominantly affects higher-order cognitive over primary sensory-motor networks, but does not appear to be specific for the default-mode or related limbic networks.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Functional brain networks, Positron emission tomography, Tau
in
Frontiers in Neuroscience
volume
11
issue
MAR
publisher
Frontiers
external identifiers
  • scopus:85017096122
  • wos:000398422500001
ISSN
1662-4548
DOI
10.3389/fnins.2017.00167
language
English
LU publication?
yes
id
09f80ff4-78a5-4168-84a7-91c466c680c2
date added to LUP
2017-05-02 10:08:56
date last changed
2018-01-07 12:01:20
@article{09f80ff4-78a5-4168-84a7-91c466c680c2,
  abstract     = {<p>Neuropathological studies have shown that the typical neurofibrillary pathology of hyperphosphorylated tau protein in Alzheimer's disease (AD) preferentially affects specific brain regions whereas others remain relatively spared. It has been suggested that the distinct regional distribution profile of tau pathology in AD may be a consequence of the intrinsic network structure of the human brain. The spatially distributed brain regions that are most affected by the spread of tau pathology may hence reflect an interconnected neuronal system. Here, we characterized the brain-wide regional distribution profile of tau pathology in AD using <sup>18</sup>F-AV 1451 tau-sensitive positron emission tomography (PET) imaging, and studied this pattern in relation to the functional network organization of the human brain. Specifically, we quantified the spatial correspondence of the regional distribution pattern of PET-evidenced tau pathology in AD with functional brain networks characterized by large-scale resting state functional magnetic resonance imaging (rs-fMRI) data in healthy subjects. Regional distribution patterns of increased PET-evidenced tau pathology in AD compared to controls were characterized in two independent samples of prodromal and manifest AD cases (the Swedish BioFINDER study, n = 44; the ADNI study, n = 35). In the BioFINDER study we found that the typical AD tau pattern involved predominantly inferior, medial, and lateral temporal cortical areas, as well as the precuneus/posterior cingulate, and lateral parts of the parietal and occipital cortex. This pattern overlapped primarily with the dorsal attention, and to some extent with higher visual, limbic and parts of the default-mode network. PET-evidenced tau pathology in the ADNI replication sample, which represented a more prodromal group of AD cases, was less pronounced but showed a highly similar spatial distribution profile, suggesting an earlier-stage snapshot of a consistently progressing regional pattern. In conclusion, the present study indicates that the regional deposition of tau aggregates in AD predominantly affects higher-order cognitive over primary sensory-motor networks, but does not appear to be specific for the default-mode or related limbic networks.</p>},
  articleno    = {167},
  author       = {Hansson, Oskar and Grothe, Michel J. and Strandberg, Tor Olof and Ohlsson, Tomas and Hägerström, Douglas and Jögi, Jonas and Smith, Ruben and Schöll, Michael},
  issn         = {1662-4548},
  keyword      = {Alzheimer's disease,Functional brain networks,Positron emission tomography,Tau},
  language     = {eng},
  month        = {03},
  number       = {MAR},
  publisher    = {Frontiers},
  series       = {Frontiers in Neuroscience},
  title        = {Tau pathology distribution in Alzheimer's disease corresponds differentially to cognition-relevant functional brain networks},
  url          = {http://dx.doi.org/10.3389/fnins.2017.00167},
  volume       = {11},
  year         = {2017},
}