Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss

Alteration of endosomal trafficking is associated with early-onset parkinsonism caused by SYNJ1 mutations

Recently, a new form of autosomal recessive early-onset parkinsonism (PARK20), due to mutations in the gene encoding the phosphoinositide phosphatase, Synaptojanin 1 (Synj1), has been reported. Several genes responsible for hereditary forms of Parkinson's disease are implicated in distinct steps of the endolysosomal pathway. However, the nature and the degree of endocytic membrane trafficking impairment in early-onset parkinsonism remains elusive. Here, we show that depletion of Synj1 causes drastic alterations of early endosomes, which become enlarged and more numerous, while it does not affect the morphology of late endosomes both in non-neuronal and neuronal cells. Moreover, Synj1 loss impairs the recycling of transferrin, while it does not alter the trafficking of the epidermal growth factor receptor. The ectopic expression of Synj1 restores the functions of early endosomes, and rescues these trafficking defects in depleted cells. Importantly, the same alterations of early endosomal compartments and trafficking defects occur in fibroblasts of PARK20 patients. Our data indicate that Synj1 plays a crucial role in regulating the homeostasis and functions of early endosomal compartments in different cell types, and highlight defective cellular pathways in PARK20. In addition, they strengthen the link between endosomal trafficking and Parkinson's disease

Comment on Numao et\ua0al.: Clinical correlates of serum insulin-like growth factor-1 in patients with Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

[no abstract available

The non-motor side of the honey-moon period of Parkinson’s disease

Objective: To explore the non-motor side of the honey-moon period in Parkinson’s disease (PD) and its impact on quality of life (QoL). Background: Although there has been increasing evidence that non-motor symptoms (NMS) are integral to PD, very little is known about NMS during the (motor) honey-moon period of PD and, to our knowledge, there are no longitudinal studies focusing on the progression of the whole NMS complex since the earliest stage, when patients receive the diagnosis and are still untreated. Methods: Consecutive, de-novo (disease duration less than 2 years and never treated with dopaminergic drugs) PD patients have been enrolled and assessed at baseline (T0) and 2 (T1) and 4 (T2) years after the enrollment. All patients were assessed with the UPDRS3 (motor scale) and the NMSQuest and completed the PDQ39, as measure of their QoL. Results: Nearly all NMS increased over time, while the motor burden remained fairly stable, indicative of an optimal (motor) response to dopaminergic drugs. Further correlations revealed the total number of NMS to be associated with QoL (rho: 0.39; p<0.01). Specifically, depression, anxiety, loss of interest and pain were the most significant factors contributing to worse QoL (Rho: 0.58, 0.52, 0.44, and 0.43 respectively, all p<0.01). No correlations were observed with motor scores. Conclusions: NMS tend to increase over the first 4 years from diagnosis in PD patients and significantly affect their QoL. Specifically, certain neuropsychiatric symptoms and pain contribute the most to worse QoL in PD patients during their "honey-moon" period

The role of Vitamin D levels on neuropsychological profile of patients with Parkinson’s Disease

even on the risk of disease development or disease progression. Only one cross-sectional study in PD patients investigated the role of vitamin D levels on neuropsychiatric functions and found that higher plasma vitamin D is associated with better cognition and better mood in PD patients without dementia. Objective: This prospective longitudinal study was performed to investigate whether low vitamin D levels at baseline are predictors of poor cognitive performances and more severe apathy and depressive symptomatology in PD patients after two years. Material and method: A sample of 48 untreated, drug-naïve PD patients was enrolled in the study. At baseline (T0), serum 25-hydroxyvitamin D and severity of motor symptoms were examined. Moreover, neuropsychological profile was assessed by cognitive tests assessing long-term memory, executive functions, visuospatial functions; Hospital Anxiety and Depression Scale (HADS) and Apathy Evaluation Scale (AES) to assess severity of depressive symptomatology and apathy. After two years (T1), 40 PD patients were evaluated and underwent the same neuropsychological battery administrated at T0. Results: At baseline, low vitamin D levels correlated significantly with poor cognitive performance on verbal immediate and delayed recall tasks, phonological fluency task, semantic fluency task, and with high score on HADS and AES. Linear regression analysis showed that low vitamin D levels contribute to poor performance on cognitive tasks assessing long-term memory, semantic fluency and high score on HADS and AES. Moreover, we found that low vitamin D level recorded at T0 correlated significantly with poor performance on immediate verbal recall, semantic fluency task, interference task of Stroop Test, and with high level of cognitive apathy evaluated at follow-up. Linear regression analysis showed that low vitamin D levels were associated significantly with poor scores on cognitive tasks assessing long-term memory, semantic fluency and with high level of cognitive apathy. Conclusions: Lower level of plasmatic vitamin D at baseline is associated with higher apathy and worse performance on cognitive tests assessing mainly frontal/executive functions at both baseline and follow-up assessment in PD. Therefore, our findings suggested that lower vitamin D levels may be a biomarker of dysexecutive syndrome in early PD patients