Regional expression of the MAPT gene is associated with loss of hubs in brain networks and cognitive impairment in Parkinson disease and progressive supranuclear palsy

NEUROBIOLOGY OF AGING

卷:48

Article

Rittman, Timothy^1,2  Rubinov, Mikail^2,3,4  Vertes, Petra E.^2,3  Patel, Ameera X.^2,3  Ginestet, Cedric E.⁵  Ghosh, Boyd C. P.⁶  Barker, Roger A.^1,2,7  Spillantini, Maria Grazia^1,7  Bullmore, Edward T.^2,3  Rowe, James B.^1,2,8 

[1] Univ Cambridge, Dept Clin Neurosci, Herchel Smith Bldg Brain & Mind Sci, Cambridge, England

[2] Univ Cambridge, Dept Psychol, Behav & Clin Neurosci Inst, Cambridge, England

[3] Dept Psychiat, Herchel Smith Bldg Brain & Mind Sci, Cambridge, England

[4] Univ Cambridge, Churchill Coll, Cambridge, England

[5] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Biostat, London, England

[6] Southampton Univ Hosp, Wessex Neurol Ctr, Southampton, Hants, England

[7] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England

[8] MRC, Cognit & Brain Sci Unit, Cambridge, England

关键词: Tau;    Progressive supranuclear palsy;    Parkinson's disease;    Gene expression;    Functional connectivity;    Brain imaging;   

DOI  :  10.1016/j.neurobiolaging.2016.09.001

来源: Elsevier

【 摘 要 】

Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects (n = 128), we examined functional brain networks and measured the connection strength between 471 gray matter regions. We obtained MAPT and SNCA microarray expression data in healthy subjects from the Allen brain atlas. Regional connectivity varied according to the normal expression of MAPT. The regional expression of MAPT correlated with the proportionate loss of regional connectivity in Parkinson's disease. Executive cognition was impaired in proportion to the loss of hub connectivity. These effects were not seen with SNCA, suggesting that alpha-synuclein pathology is not mediated through global network properties. The results establish a link between regional MAPT expression and selective vulnerability of functional brain networks to neurodegeneration. (C) 2016 The Authors. Published by Elsevier Inc.

【 授权许可】

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