title: Structural imaging in the presymptomatic stage of genetically determined parkinsonism.
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.
authors.affiliation: Department of Neurology, RWTH Aachen University, Aachen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reetz
authors.forename: Vera
authors.initials: V
authors.lastname: Tadic
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ramirez
authors.forename: Maria I
authors.initials: MI
authors.lastname: Behrens
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Binkofski
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000235:genetics / Q000473:pathology*; D018579:Patient Selection; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D006180:Proton-Translocating ATPases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D006180:Proton-Translocating ATPases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C514983:ATP13A2 protein, human; C111567:parkin protein; C495280:LRRK2 protein, human