Abstract
Understanding the role of Tau protein aggregation in the pathogenesis of Alzheimer's disease is critical for the development of new Tau-based therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography with [18F]AV-1451 PET scanning to quantify Tau-dependent network changes. Using a graph theoretical approach to brain connectivity, we quantified nodal measures of functional segregation, centrality, and the efficiency of information transfer and tested them against levels of [18F]AV-1451. Higher Tau burden in early Alzheimer's disease was associated with a shift away from the optimal small-world organization and a more fragmented network in the beta and gamma bands, whereby parieto-occipital areas were disconnected from the anterior parts of the network. Similarly, higher Tau burden was associated with decreases in both local and global efficiency, especially in the gamma band. The results support the translational development of neurophysiological “signatures” of Alzheimer's disease, to understand disease mechanisms in humans and facilitate experimental medicine studies.
Original language | English |
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Pages (from-to) | 141-152 |
Number of pages | 12 |
Journal | Neurobiology of Aging |
Volume | 92 |
DOIs | |
Publication status | Published - Aug 2020 |
Bibliographical note
Funding Information:The Deep and Frequent Phenotyping Study is funded by the Medical Research Council , United Kingdom and National Institute for Health Research as part of the Dementias Platform UK (MR/N029941/1). JBR is supported by the Wellcome Trust , United Kingdom ( 103838 ); Medical Research Council (SUAG/004 RG91365) and National Institute for Health Research Cambridge Biomedical Research Centre. RH is supported by the Medical Research Council (SUAG/010 RG91365). MWW's research is supported by the NIHR Oxford Health Biomedical Research Centre, the Wellcome Trust (106183/Z/14/Z and 203139/Z/16/Z) and the MRC UK MEG Partnership Grant (MR/K005464/1). EK is funded by the Dementias Platform UK and Alzheimer's Research UK (RG94383/RG89702). The authors thank all participants and their families, the PET technicians, radiochemists, the MRI radiographers, and the clinical research nurses for their cooperation and support of this study. They thank Avid radiopharmaceuticals for the provision of [ 18 F]AV-1451 doses and Wellcome Centre for Human Neuroimaging at University College London for their support with MEG scans. The authors thank Dr Rezvan Farahibozorg and Dr Timothy Rittman for useful discussions about the analyses and methods.
Funding Information:
The Deep and Frequent Phenotyping Study is funded by the Medical Research Council, United Kingdom and National Institute for Health Research as part of the Dementias Platform UK (MR/N029941/1). JBR is supported by the Wellcome Trust, United Kingdom (103838); Medical Research Council (SUAG/004 RG91365) and National Institute for Health Research Cambridge Biomedical Research Centre. RH is supported by the Medical Research Council (SUAG/010 RG91365). MWW's research is supported by the NIHR Oxford Health Biomedical Research Centre, the Wellcome Trust (106183/Z/14/Z and 203139/Z/16/Z) and the MRC UK MEG Partnership Grant (MR/K005464/1). EK is funded by the Dementias Platform UK and Alzheimer's Research UK (RG94383/RG89702). The authors thank all participants and their families, the PET technicians, radiochemists, the MRI radiographers, and the clinical research nurses for their cooperation and support of this study. They thank Avid radiopharmaceuticals for the provision of [18F]AV-1451 doses and Wellcome Centre for Human Neuroimaging at University College London for their support with MEG scans. The authors thank Dr Rezvan Farahibozorg and Dr Timothy Rittman for useful discussions about the analyses and methods. Author's contributions: SL, JBR, RNH, GG, GB, MWW, and RG designed the experiment. AQ, EC, and AG. collected the E/MEG data. AF preprocessed the PET and MR data. EK preprocessed the MEG data and performed the data analysis. EK and JBR wrote the manuscript, and all authors contributed to the final version.
Publisher Copyright:
© 2020 The Authors
Keywords
- Alzheimer's disease
- Connectivity
- Graph theory
- MEG
- PET
- Tau
ASJC Scopus subject areas
- General Neuroscience
- Ageing
- Developmental Biology
- Clinical Neurology
- Geriatrics and Gerontology