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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

Rittman, Timothy; Rubinov, Mikail; Vértes, Petra E; Patel, Ameera X; Ginestet, Cedric E; Ghosh, Boyd C P; Barker, Roger A LU ; Spillantini, Maria Grazia; Bullmore, Edward T and Rowe, James B (2016) In Neurobiology of Aging 48. p.153-160
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson disease, supranuclear palsy, MAPT gene
in
Neurobiology of Aging
volume
48
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:84988937286
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2016.09.001
language
English
LU publication?
yes
id
17c3cb49-21b2-4638-8f9a-1bd74d851397
date added to LUP
2016-11-23 13:02:11
date last changed
2017-07-30 05:17:41
@article{17c3cb49-21b2-4638-8f9a-1bd74d851397,
  abstract     = {<p>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.</p>},
  author       = {Rittman, Timothy and Rubinov, Mikail and Vértes, Petra E and Patel, Ameera X and Ginestet, Cedric E and Ghosh, Boyd C P and Barker, Roger A and Spillantini, Maria Grazia and Bullmore, Edward T and Rowe, James B},
  issn         = {0197-4580},
  keyword      = {Parkinson disease,supranuclear palsy,MAPT gene},
  language     = {eng},
  month        = {09},
  pages        = {153--160},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.001},
  volume       = {48},
  year         = {2016},
}