Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: A mendelian randomization study

Author(s):  
Mengmeng Wang ◽  
Zhizhong Zhang ◽  
Dandan Liu ◽  
Lei Ji ◽  
Shuangjiao Huang ◽  
...  
2014 ◽  
Vol 14 (3) ◽  
pp. 310-321 ◽  
Author(s):  
Zhiming Li ◽  
Qing Lin ◽  
Qilin Ma ◽  
Congxia Lu ◽  
Chi-Meng Tzeng

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 772
Author(s):  
João Botelho ◽  
Vanessa Machado ◽  
José João Mendes ◽  
Paulo Mascarenhas

The latest evidence revealed a possible association between periodontitis and Parkinson’s disease (PD). We explored the causal relationship of this bidirectional association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on periodontitis and PD. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and eight non-overlapping SNPs of periodontitis from an additional GWAS for validation purposes. Instrumental variables to explore for the reverse causation included forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B = −0.0003, Standard Error [SE] 0.0003, p = 0.26). The eight independent SNPs (B = −0.0000, SE 0.0001, p = 0.99) validated this outcome. We also found no association of genetically primed PD towards periodontitis (B = −0.0001, SE 0.0001, p = 0.19). These MR study findings do not support a bidirectional causal genetic liability between periodontitis and PD. Further GWAS studies are needed to confirm the consistency of these results.


2018 ◽  
Vol 19 (S1) ◽  
Author(s):  
Zhifa Han ◽  
Rui Tian ◽  
Peng Ren ◽  
Wenyang Zhou ◽  
Pingping Wang ◽  
...  

Brain ◽  
2020 ◽  
Vol 143 (3) ◽  
pp. 920-931 ◽  
Author(s):  
Samanta Mazzetti ◽  
Milo J Basellini ◽  
Valentina Ferri ◽  
Erica Cassani ◽  
Emanuele Cereda ◽  
...  

Abstract A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson’s disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson’s disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson’s disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson’s disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson’s disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson’s disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.


2020 ◽  
Vol 88 (5) ◽  
pp. 1043-1047
Author(s):  
Dylan M. Williams ◽  
Sara Bandres‐Ciga ◽  
Karl Heilbron ◽  
David Hinds ◽  
Alastair J. Noyce ◽  
...  

2021 ◽  
Vol 6 (3) ◽  
pp. 78-84
Author(s):  
D. S. Yaroshenko ◽  

The review article presents data on the history of research of extrapyramidal system dysfunctions, modern ideas about the etiology and diagnosis of Parkinson's disease, as the most common disease of the group of extrapyramidal disorders. Currently, no concept of effective therapy for patients with extrapyramidal system dysfunction has been developed, but it has been proven that the probability of developing the disease largely depends on the genetic predisposition and the level of environmental pollution. In the early stages, the disease is slow and asymptomatic, but gradually more than half of patients with Parkinson's disease die, and others need outside care. According to experts, in the near future, Parkinson's disease will become a problem for a significant part of people, because today it affects more and more people of working age. Under such conditions, reliable and early diagnosis of the disease is of great importance, which guarantees timely and most effective treatment. Modern therapies fail to stop the progressive death of the dopaminergic neurons of the substantia nigra, but traditional treatment can achieve symptomatic relief. Currently, it is known that the probability of developing Parkinson's disease depends on the genetic predisposition and the level of man-made environmental stress. The researchers consider that the pathological development of Parkinson's disease in the brain begins in the lower structures of the brain stem with the involvement of the caudal-Rostral nuclei, as well as the involvement of the cortico-basal ganglia-cerebellar pathways. The pathological process affects the ascending pathways and gradually passes to the midbrain, directly to the black substance, spreads from there and weakens the mesocortex and neocortex. Injuries in the brain stem lead to disorganization of the cortico-basal ganglia and cerebellar pathways, followed by the formation of alternative pathways to compensate for the initial disorders in the early stages of the disease. In addition, in Parkinson's disease, intracellular Lewy bodies and neurites formed by the protein alpha-synuclein are created, which are found in the autopsy material of most patients. Poor results of diagnostic evaluation and treatment of Parkinson's disease are usually associated with a lack of understanding of the pathogenesis of Parkinson's disease. The study of the biological basis and pathogenesis of Parkinson's disease is an important task of a whole complex of scientific studies of extrapyramidal system dysfunction. Conclusion. The article discusses the creation of toxic models of Parkinson's disease in vivo and in vitro, which help to recreate the pathogenesis of the disease for early diagnosis and the development of new ways to treat neurodegenerative diseases. In toxic models of Parkinsonism, not only deficits of motor functions such as bradykinesia, tremor, and posture disorders are actively studied, but also non-motor symptoms such as sleep disorders, neuropsychiatric and cognitive abnormalities


Sign in / Sign up

Export Citation Format

Share Document