Structural imaging in the presymptomatic stage of genetically determined parkinsonism

Neurobiol Dis. 2010 Sep;39(3):402-8. doi: 10.1016/j.nbd.2010.05.006. Epub 2010 May 17.

Abstract

Several genes associated with monogenic forms of Parkinson's disease (PD) have been discovered, opening up new avenues for the investigation of presymptomatic stages of PD. Using voxel-based morphometry in 30 asymptomatic mutation carriers (MC) with mutations in four different genes for PD and 100 healthy controls, we identified an increase in gray matter volume (GMV) in the striatum in asymptomatic Parkin, PINK1, ATP13A2 and, to a much lesser extent, in LRRK2 MC. Moreover, an increase in GMV was found in the parieto-temporo-occipital association cortex in asymptomatic Parkin and ATP13A2 MC. The observed striatal GMV increase might be the common structural correlate of compensatory mechanisms due to the latent dopaminergic deficit, reflecting the different, but probably interrelated pathogenic pathways resulting in nigral cell death. Asymptomatic PINK1 and LRRK2 MC also revealed smaller GMV in the hippocampal region, which might play a role in the observed psychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Magnetic Resonance Imaging
  • Middle Aged
  • Nerve Fibers, Unmyelinated / pathology*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / pathology*
  • Patient Selection
  • Protein Kinases / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Proton-Translocating ATPases / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • ATP13A2 protein, human
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • Proton-Translocating ATPases