Parkinson's disease in twins studied with ¹⁸ F‐dopa and positron emission tomography

Abstract

We used 18F-dopa PET to examine concordance for dysfunction of the nigrostriatal dopaminergic system in 18 co-twins of patients with Parkinson's disease (PD) and scanned one clinically concordant monozygotic (MZ) twin pair, 17 asymptomatic co-twins (10 MZ, 7 dizygotic [DZ]), and 13 twins with PD (8 MZ, 5 DZ). Mean 18F-dopa uptake of the twins with PD was significantly reduced in putamen to 38% and in caudate to 66% of normal. Mean putamen 18F-dopa uptake for the 17 asymptomatic co-twins was also significantly reduced (86% of normal), as was putamen tracer uptake for the 10 MZ (87% of normal) and seven DZ (83% of normal) asymptomatic co-twin subgroups. Four of 10 MZ and two of seven DZ asymptomatic co-twins had putamen 18F-dopa uptake reduced more than 2 SDs below the normal mean. Three of these four asymptomatic MZ co-twins had tremor on examination at the time of PET and one has now developed PD 2 years later. Our PET findings give concordances for nigral dysfunction of 45% in the MZ pairs and 29% in the DZ pairs at a 2-SD threshold, and 18% in MZ and 0% in DZ pairs at a 3-SD threshold of significance. These data suggest that the concordance for nigral pathology in PD twins may be higher than previously realized and that the presence of an isolated postural or rest tremor may be a phenotypic expression of PD.

Genome-wide association study confirms extant PD risk loci among the Dutch

“…A genetic contribution to Parkinson's disease (PD) is well recognized [1][2][3] with B10% of the cases carrying mutations that lead to rare Mendelian forms of the disease. 4 Recently, independent genomewide association studies (GWAS) established an unequivocal role for common genetic variants in the etiology of PD [5][6][7][8][9][10][11] and suggested a population-specific genetic heterogeneity, with SNCA, PARK16, BST1 and LRRK2 as shared risk loci for PD, [6][7][8]10,11 and MAPT as an European-specific risk locus.…”

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

“…Studies using positron emission tomography (PET) scanning have demonstrated that the onset of PD symptoms is preceded by a period -estimated at five to six years on average -of impaired dopaminergic function in the striatum [121]. When the procedure was applied in a twin study to assess nigrostriatal dysfunction instead of clinically diagnosed PD, concordance rates were 45% in monozygotic twins versus 29% in dizygotic twins [122].…”

Rural or urban living and Parkinson's disease

“…It is known that PD does not generally show hereditary characteristics but some cases have shown clear autosomic dominant transmission with reduced penetrance 14 . Identical twin studies have shown low PD concordance 19 , although PET scan studies on twins using fluorodopa demonstrated that the non-parkinsonian twins have a greater tendency towards nigral dysfunction 3 . Barbeau et al 1 were the first to call attention to the possibility that a combination of genetic and environmental factors may be responsible for the origin of the disease.…”