Structural imaging in the presymptomatic stage of genetically determined parkinsonism

TY - JOUR

T1 - Structural imaging in the presymptomatic stage of genetically determined parkinsonism

AU - Reetz, Kathrin

AU - Tadic, Vera

AU - Kasten, Meike

AU - Brüggemann, Norbert

AU - Schmidt, Alexander

AU - Hagenah, Johann

AU - Pramstaller, Peter P

AU - Ramirez, Alfredo

AU - Behrens, Maria I

AU - Siebner, Hartwig R

AU - Klein, Christine

AU - Binkofski, Ferdinand

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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.

AB - 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.

KW - Adult

KW - Brain

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Magnetic Resonance Imaging

KW - Middle Aged

KW - Nerve Fibers, Unmyelinated

KW - Parkinsonian Disorders

KW - Patient Selection

KW - Protein Kinases

KW - Protein-Serine-Threonine Kinases

KW - Proton-Translocating ATPases

KW - Ubiquitin-Protein Ligases

U2 - 10.1016/j.nbd.2010.05.006

DO - 10.1016/j.nbd.2010.05.006

M3 - Journal article

C2 - 20483373

SN - 0969-9961

VL - 39

SP - 402

EP - 408

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 3

ER -