Imaging the impact of genes on Parkinson's disease
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Imaging the impact of genes on Parkinson's disease. / van der Vegt, J P M; van Nuenen, B F L; Bloem, B R; Klein, C; Siebner, H R.
In: Neuroscience, Vol. 164, No. 1, 2009, p. 191-204.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Imaging the impact of genes on Parkinson's disease
AU - van der Vegt, J P M
AU - van Nuenen, B F L
AU - Bloem, B R
AU - Klein, C
AU - Siebner, H R
N1 - Keywords: Animals; Brain; Genetic Variation; Humans; Parkinson Disease
PY - 2009
Y1 - 2009
N2 - Although Parkinson's disease (PD) has traditionally been considered to be a non-genetic disorder, recent progress in the neurogenetics of PD provided converging evidence that genetic factors play a relevant role in the etiology of PD. The strongest case for a genetic contribution to PD was made by the discovery of mutations in single genes that can cause autosomal dominant (alpha-synuclein (SNCA)) and leucine rich repeat kinase 2 (LRRK2) gene) or recessive (Parkin, PTEN-induced putative kinase 1 (PINK1), DJ-1, and ATP13A2 gene) forms of PD. Here, we review how structural and functional neuroimaging of individuals carrying a mutation in one of the PD genes has offered a unique avenue of research into the pathogenesis of PD. In symptomatic mutation carriers (i.e. those with overt disease), brain mapping can help to link the molecular pathogenesis of PD more directly with functional and structural changes in the intact human brain. In addition, neuroimaging of presymptomatic (i.e. non-manifesting) mutation carriers has emerged as a valuable tool to identify mechanisms of adaptive motor reorganization at the preclinical stage that may prevent or delay clinical manifestation. In addition to mutations causing monogenic forms of PD, common polymorphisms in genes that influence mono-aminergic signaling or synaptic plasticity may have modifying effects on distinct aspects of PD. We also discuss how functional and structural neuroimaging can be used to better characterize these genotype-phenotype correlations.
AB - Although Parkinson's disease (PD) has traditionally been considered to be a non-genetic disorder, recent progress in the neurogenetics of PD provided converging evidence that genetic factors play a relevant role in the etiology of PD. The strongest case for a genetic contribution to PD was made by the discovery of mutations in single genes that can cause autosomal dominant (alpha-synuclein (SNCA)) and leucine rich repeat kinase 2 (LRRK2) gene) or recessive (Parkin, PTEN-induced putative kinase 1 (PINK1), DJ-1, and ATP13A2 gene) forms of PD. Here, we review how structural and functional neuroimaging of individuals carrying a mutation in one of the PD genes has offered a unique avenue of research into the pathogenesis of PD. In symptomatic mutation carriers (i.e. those with overt disease), brain mapping can help to link the molecular pathogenesis of PD more directly with functional and structural changes in the intact human brain. In addition, neuroimaging of presymptomatic (i.e. non-manifesting) mutation carriers has emerged as a valuable tool to identify mechanisms of adaptive motor reorganization at the preclinical stage that may prevent or delay clinical manifestation. In addition to mutations causing monogenic forms of PD, common polymorphisms in genes that influence mono-aminergic signaling or synaptic plasticity may have modifying effects on distinct aspects of PD. We also discuss how functional and structural neuroimaging can be used to better characterize these genotype-phenotype correlations.
U2 - 10.1016/j.neuroscience.2009.01.055
DO - 10.1016/j.neuroscience.2009.01.055
M3 - Journal article
C2 - 19409223
VL - 164
SP - 191
EP - 204
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 1
ER -
ID: 21456519