Regional expression of genes mediating trans-synaptic alpha-synuclein transfer predicts regional atrophy in Parkinson disease Academic Article Article uri icon

Overview

MeSH Major

  • Algorithms
  • Image Enhancement
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Signal Processing, Computer-Assisted

abstract

  • © 2018 The Author(s) Multiple genes have been implicated in Parkinson disease pathogenesis, but the relationship between regional expression of these genes and regional dysfunction across the brain is unknown. We address this question by joint analysis of high resolution magnetic resonance imaging data from the Parkinson's Progression Markers Initiative and regional genetic microarray expression data from the Allen Brain Atlas. Regional brain atrophy and genetic expression was co-registered to a common 86 region brain atlas and robust multivariable regression analysis was performed to identify genetic predictors of regional brain atrophy. Top candidate genes from GWAS analysis, as well as genes implicated in trans-synaptic alpha-synuclein transfer and autosomal recessive PD were included in our analysis. We identify three genes with expression patterns that are highly significant predictors of regional brain atrophy. The two most significant predictors are LAG3 and RAB5A, genes implicated in trans-synaptic synuclein transfer. Other well-validated PD-related genes do not have expression patterns that predict regional atrophy, suggesting that they may serve other roles such as disease initiation factors.

publication date

  • January 2018

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/j.nicl.2018.01.009

PubMed ID

  • 29868450

Additional Document Info

start page

  • 456

end page

  • 466

volume

  • 18