A case‐control study of twin pairs discordant for Parkinson's disease

Bharucha, Nadir E.; Stokes, Lynette; Schoenberg, Bruce S.; Ward, Christopher; Ince, Susan; Nutt, John G.; Eldridge, Roswell; Calne, Donald B.; Mantel, Nathan; Duvoisin, Roger C.

doi:10.1212/wnl.36.2.284

Cited by 87 publications

(46 citation statements)

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“…The aggregated MZ\DZ concordance ratio of 1.2 : 1 found in previous twin studies provided no evidence of a significant genetic risk (Ward et al 1983 ;Barucha et al 1986 ;Marsden, 1987 ;Tanner, 1992 ;Vieregge et al 1992). However, these cross-sectional studies do not allow detection of cases with subclinical disease.…”

Section: Twin Studies and The Role Of Positron Emission Tomographymentioning

confidence: 81%

Genetics of Parkinsonism: a review

VAUGHAN¹,

DAVIS²,

WOOD³

2001

Annals of Human Genetics

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Idiopathic Parkinson's disease (IPD), a progressive neurodegenerative disorder, is a common cause of disability. No current therapies modify disease progression. The pathological hallmarks are the presence of Lewy bodies and massive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Two genes (SNCA and parkin) as well as two gene loci have now been implicated in the pathogenesis of familial PD. These represent significant progress in our understanding of the disease, considering the rarity of large families, low heritability in the general population and genetic heterogeneity. Mutations in a further gene, UCHL1, have been described in familial PD although the evidence for its role in PD is less clear. Knowledge of the genes described in PD to date should help to define molecular mechanisms of neurodegeneration in PD, as well as in other diseases where defects in protein handling may be a common feature. Nigral degeneration with Lewy body formation and the resulting clinical picture of PD may represent a final common pathway of a multifactorial disease process in which both environmental and genetic factors have a role. This review discusses the major advances in the field to date and illustrates how the existence of genetic factors has now become firmly established.

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Section: Twin Studies and The Role Of Positron Emission Tomographymentioning

confidence: 81%

Genetics of Parkinsonism: a review

VAUGHAN¹,

DAVIS²,

WOOD³

2001

Annals of Human Genetics

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“…A Chinese study reported lower PD risk associated with regular liquor drinking (OR 0.28, 95% CI 0.12-0.65) [146]. In a small co-twin controlled study of 31 monozygotic twin pairs, the unaffected twin drank more alcohol than the affected twin, corresponding to a RR of 0.5 [426].…”

Section: Case-control Studiesmentioning

confidence: 98%

“…Most of these studies included men only. Two small co-twin controlled studies reported a statistically non-significant inverse association between smoking and PD [425,426]. A somewhat larger co-twin controlled study reported that in twin pairs discordant for PD, the unaffected twin smoked more (in pack-years) than the affected twin [427].…”

Section: Smokingmentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…However, not all epidemiological studies have been able to demonstrate a statistically significant link between TBI and PD; some studies show a strong correlation (Bower et al, 2003;Goldman et al, 2006;Taylor et al, 1999), while others do not (Bharucha et al, 1986;Rugbjerg et al, 2008;Werneck and Alvarenga, 1999). These observations suggest that the link between TBI and PD may be contingent upon exposure to other risk factors, with TBI being one element sensitizing neurons to other risk factors, as suggested in the ''multiple hits'' hypothesis of PD (Sulzer, 2007).…”

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confidence: 97%

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

Hutson

Lazo

Mortazavi

et al. 2011

Journal of Neurotrauma

117

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. In an acute study, rats received moderate TBI by lateral fluid percussion (LFP) injury, were injected with saline or paraquat (10 mg/kg IP) 3 and 6 days after LFP, were sacrificed 5 days later, and their brains processed for immunohistochemistry. TBI alone increased microglial activation in the substantia nigra, and caused a 15% loss of dopaminergic neurons ipsilaterally. Paraquat increased the TBI effect, causing a 30% bilateral loss of dopaminergic neurons, reduced striatal tyrosine hydroxylase (TH) immunoreactivity more than TBI alone, and induced alpha-synuclein accumulation in the substantia nigra pars compacta. In a long-term study, rats received moderate LFP, were injected with saline or paraquat at 21 and 22 weeks post-injury, and were sacrificed 4 weeks later. At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk.

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A case‐control study of twin pairs discordant for Parkinson's disease

Cited by 87 publications

References 0 publications

Genetics of Parkinsonism: a review

Genetics of Parkinsonism: a review

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

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