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Tau-related grey matter network breakdown across the Alzheimer’s disease continuum

Pelkmans, Wiesje LU ; Ossenkoppele, Rik LU ; Dicks, Ellen ; Strandberg, Olof LU ; Barkhof, Frederik ; Tijms, Betty M. ; Pereira, Joana B. LU and Hansson, Oskar LU orcid (2021) In Alzheimer's Research and Therapy 13(1).
Abstract

Background: Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum. Methods: We included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive... (More)

Background: Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum. Methods: We included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive patients with mild cognitive impairment, and 128 patients with AD dementia) from the BioFINDER-2 study. Single-subject grey matter networks were extracted from T1-weighted images and graph theory properties including degree, clustering coefficient, path length, and small world topology were calculated. Associations between tau positron emission tomography (PET) values and global and regional network measures were examined using linear regression models adjusted for age, sex, and total intracranial volume. Finally, we tested whether the association of tau pathology with cognitive performance was mediated by grey matter network disruptions. Results: Across the whole sample, we found that higher tau load in the temporal meta-ROI was associated with significant changes in degree, clustering, path length, and small world values (all p < 0.001), indicative of a less optimal network organisation. Already in CU Aβ-positive individuals associations between tau burden and lower clustering and path length were observed, whereas in advanced disease stages elevated tau pathology was progressively associated with more brain network abnormalities. Moreover, the association between higher tau load and lower cognitive performance was only partly mediated (9.3 to 9.5%) through small world topology. Conclusions: Our data suggest a close relationship between grey matter network disruptions and tau pathology in individuals with abnormal amyloid. This might reflect a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions with tau pathology, indicative of a more random network topology across different AD stages.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Graph theory, Grey matter network, MRI, PET, Tau
in
Alzheimer's Research and Therapy
volume
13
issue
1
article number
138
publisher
BioMed Central (BMC)
external identifiers
  • pmid:34389066
  • scopus:85112478733
ISSN
1758-9193
DOI
10.1186/s13195-021-00876-7
language
English
LU publication?
yes
id
203776a8-4090-40fb-86a3-e7679e6b8039
date added to LUP
2021-09-06 10:23:28
date last changed
2024-04-06 08:14:25
@article{203776a8-4090-40fb-86a3-e7679e6b8039,
  abstract     = {{<p>Background: Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum. Methods: We included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive patients with mild cognitive impairment, and 128 patients with AD dementia) from the BioFINDER-2 study. Single-subject grey matter networks were extracted from T1-weighted images and graph theory properties including degree, clustering coefficient, path length, and small world topology were calculated. Associations between tau positron emission tomography (PET) values and global and regional network measures were examined using linear regression models adjusted for age, sex, and total intracranial volume. Finally, we tested whether the association of tau pathology with cognitive performance was mediated by grey matter network disruptions. Results: Across the whole sample, we found that higher tau load in the temporal meta-ROI was associated with significant changes in degree, clustering, path length, and small world values (all p &lt; 0.001), indicative of a less optimal network organisation. Already in CU Aβ-positive individuals associations between tau burden and lower clustering and path length were observed, whereas in advanced disease stages elevated tau pathology was progressively associated with more brain network abnormalities. Moreover, the association between higher tau load and lower cognitive performance was only partly mediated (9.3 to 9.5%) through small world topology. Conclusions: Our data suggest a close relationship between grey matter network disruptions and tau pathology in individuals with abnormal amyloid. This might reflect a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions with tau pathology, indicative of a more random network topology across different AD stages.</p>}},
  author       = {{Pelkmans, Wiesje and Ossenkoppele, Rik and Dicks, Ellen and Strandberg, Olof and Barkhof, Frederik and Tijms, Betty M. and Pereira, Joana B. and Hansson, Oskar}},
  issn         = {{1758-9193}},
  keywords     = {{Alzheimer’s disease; Graph theory; Grey matter network; MRI; PET; Tau}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Tau-related grey matter network breakdown across the Alzheimer’s disease continuum}},
  url          = {{http://dx.doi.org/10.1186/s13195-021-00876-7}},
  doi          = {{10.1186/s13195-021-00876-7}},
  volume       = {{13}},
  year         = {{2021}},
}