scholarly journals Frequency of Heterozygous Parkin (PRKN) Variants and Penetrance of Parkinson's Disease Risk Markers in the Population-Based CHRIS Cohort

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Paulina Castelo Rueda ◽  
Athina Raftopoulou ◽  
Martin Gögele ◽  
Max Borsche ◽  
David Emmert ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Symptoms ◽  
Large Population ◽  
Population Sample ◽  
Genotype Imputation ◽  
Carrier Status ◽  
Risk Markers ◽  
Mutation Carriers ◽  
Increased Risk

Mutations in the Parkin (PRKN) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous PRKN mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimates of the penetrance of these variants, and to investigate, which clinical and biochemical markers are present in carriers and thus potentially useful for identifying those individuals at greater risk of developing clinical symptoms later in life. In the present study, we ascertained the frequency of heterozygous PRKN mutation carriers in a large population sample of the Cooperative Health Research in South Tyrol (CHRIS) study, and screened for reported PD risk markers. 164 confirmed heterozygous PRKN mutation carriers were compared with 2,582 controls. A higher number of heterozygous mutation carriers reported a detectable increase in an akinesia-related phenotype, and a higher percentage of carriers had manifested diabetes. We also observed lower resting heart rate in the PRKN mutation carriers. Extending our risk analyses to a larger number of potential carriers and non-carriers using genotype imputation (n = 299 carriers and n = 7,127 non-carriers), from previously published biomarkers we also observed a higher neutrophil-to-lymphocyte ratio (NLR) and lower serum albumin and sodium levels in the heterozygous PRKN variant carriers. These results identify a set of biomarkers that might be useful either individually or as an ensemble to identify variant carriers at greater risk of health issues due to carrier status.

LRRK2, GBA and SMPD1 Founder Mutations and Parkinson's Disease in Ashkenazi Jews

2016 ◽  
Vol 42 (1-2) ◽  
pp. 1-6 ◽  
Author(s):  
Efrat Dagan ◽  
Ilana Schlesinger ◽  
Alina Kurolap ◽  
Mareemar Ayoub ◽  
Maria Nassar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Statistical Significance ◽  
Clinical Manifestations ◽  
Age At Diagnosis ◽  
Carrier Status ◽  
Ashkenazi Jews ◽  
Founder Mutations ◽  
Mutation Carriers

Background/Aim: Parkinson's disease (PD) is associated with mutations in LRRK2, GBA, and SMPD1 genes. We describe the clinical characteristics of PD patients related to their carrier status of the Ashkenazi founder mutations in the aforementioned genes. Methods: Ashkenazi PD patients (n = 270) were recruited following informed consent, and tested for the founder Ashkenazi mutations in the above genes. Clinical characteristics were compared between carriers and noncarriers. Homozygotes for mutations in GBA or LRRK2, and those who carried mutations in two causative genes were excluded from the analysis. Results: Five (1.85%), 54 (20%), and 22 (8.1%) PD patients carried mutations in SMPD1, GBA or LRRK2, respectively. By post hoc Bonferroni analysis, GBA carriers were singled at a significantly earlier age at diagnosis compared to noncarriers (58.06 ± 10.84 and 62.65 ± 10.86 years, respectively; p = 0.036), and due to bilateral manifestation at diagnosis compared to all other PD groups (n = 8, 15.7% compared to n = 2, 1.1%, respectively; p < 0.001). Other clinical manifestations were comparable between groups. Conclusion: Although only GBA mutation carriers, compared to noncarriers, reached statistical significance regarding age at diagnosis, it appears that LRRK2 and SMPD1 mutation carriers may reach significance with larger group numbers.

Parkinson’s puzzle

2012 ◽  
Vol 153 (52) ◽  
pp. 2060-2069 ◽  
Author(s):  
András Guseo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Symptoms ◽  
Critical Factor ◽  
Unknown Origin ◽  
Symptomatic Improvement ◽  
Blue Green Algae ◽  
Clinical Observations ◽  
Degenerative Disorders ◽  
Local Cell

Parkinson’s disease is one of the most frequent progressive degenerative disorders with unknown origin of the nervous system. The commutation of the disease on Guam led to the discovery of a neurotoxin which was also found in other continents. This neurotoxin was identified in the common cyanobacteria (blue-green algae). Early clinical observations suggested some loose correlations with gastric and duodenal ulcer and Parkinson’s disease, while recent studies revealed a toxin, almost identical to that found in cyanobacteria in one strain of Helicobacter pylori, which proved to cause Parkinson like symptoms in animals. Therefore, it cannot be ruled out that there is a slowly progressive poisoning in Parkinson’s disease. The disease specific alpha-sinuclein inclusions can be found in nerve cells of the intestinal mucosa far before the appearance of clinical symptoms indicating that the disease may start in the intestines. These results are strengthened by the results of Borody’s fecal transplants, after which in Parkinson patients showed a symptomatic improvement. Based on these observations the Parkinson puzzle is getting complete. Although these observations are not evidence based, they may indicate a new way for basic clinical research, as well as a new way of thinking for clinicians. These new observations in psycho-neuro-immunology strengthen the fact that immunological factors may also play a critical factor facilitating local cell necrosis which may be influenced easily. Orv. Hetil., 2012, 153, 2060–2069.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

scholarly journals A-079 Hand Preference in Men and Women with Parkinson’s Disease: A Preliminary Investigation

2020 ◽  
Vol 35 (6) ◽  
pp. 871-871
Author(s):  
Ryan J ◽  
Kreiner D ◽  
Gontkovsky S ◽  
Paolo A
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurological Disorders ◽  
Rating Scale ◽  
Preliminary Investigation ◽  
Hand Preference ◽  
Dominant Hand ◽  
Healthy Individuals ◽  
Left Handed ◽  
Increased Risk

Abstract Objective Research has identified common genetic influences on handedness and neurological/mental health phenotypes. It also has been shown there may be increased risk for development of neurological disorders/diseases among individuals naturally left-handed or demonstrating non-right-hand preference. This investigation examined prevalence of right-handed versus non-right-handed individuals with Parkinson’s disease (PD) compared to controls. Method Participants were 264 patients with PD (mean age = 69.83 years) and 256 control volunteers (mean age = 71.42 years). Mean Dementia Rating Scale composites for the groups were 123.68 and 136.00, respectively. Participants self-identified their dominant hand for writing and usage was confirmed during the session. Results Proportions of non-right- and right-handed controls (7.0% and 93.0%) versus individuals with PD (6.8% and 93.2%) did not differ. Changes in proportions of non-right- and right-handedness across age ranges were not significant for controls or patients. There was a trend for a larger proportion of women (55.9%) versus men among controls (44.1%), □ 2 (1) = 3.29, p &lt; .10; whereas, the proportion of men (64.4%) with PD was larger than that of women. (35.6%), □ 2 (1) = 21.31, p &lt; .001. For controls and patients, non-right and right handedness gender proportions were similar. Conclusions This study is the first to assess handedness prevalence rates in PD. Results suggest prevalence of non-right handedness is similar in PD and healthy individuals and does not appear to differ markedly by gender or with advancing age. The occurrence of a trend for a larger proportion of women than men among controls is consistent with census-based statistics.

Migraine is related to an increased risk of Parkinson’s disease: A population-based, propensity score-matched, longitudinal follow-up study

Cephalalgia ◽  
2016 ◽  
Vol 36 (14) ◽  
pp. 1316-1323 ◽  
Author(s):  
Hsin-I Wang ◽  
Yu-Chun Ho ◽  
Ya-Ping Huang ◽  
Shin-Liang Pan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Survival Rate ◽  
Propensity Score ◽  
Population Based ◽  
Free Survival ◽  
Follow Up Study ◽  
Increased Risk ◽  
Migraine Group

Background The association between migraine and Parkinson’s disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. Methods A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan–Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. Results During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25–2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group ( p = 0.0041). Conclusions This study showed an increased risk of developing PD in patients with migraine.

scholarly journals Therapeutic Effects of Hydrogen in Animal Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Yusaku Nakabeppu ◽  
Mami Noda
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Animal Studies ◽  
Clinical Symptoms ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
6 Hydroxydopamine

Since the first description of Parkinson's disease (PD) nearly two centuries ago, a number of studies have revealed the clinical symptoms, pathology, and therapeutic approaches to overcome this intractable neurodegenerative disease. 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are neurotoxins which produce Parkinsonian pathology. From the animal studies using these neurotoxins, it has become well established that oxidative stress is a primary cause of, and essential for, cellular apoptosis in dopaminergic neurons. Here, we describe the mechanism whereby oxidative stress evokes irreversible cell death, and propose a novel therapeutic strategy for PD using molecular hydrogen. Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.

Different saccadic abnormalities in PINK1 mutation carriers and in patients with non-genetic Parkinson’s disease

2009 ◽  
Vol 256 (7) ◽  
pp. 1192-1194 ◽  
Author(s):  
Susanne Hertel ◽  
Andreas Sprenger ◽  
Christine Klein ◽  
Detlef Kömpf ◽  
Christoph Helmchen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mutation Carriers

scholarly journals Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case–control study in Japan

2010 ◽  
Vol 104 (5) ◽  
pp. 757-764 ◽  
Author(s):  
Kentaro Murakami ◽  
Yoshihiro Miyake ◽  
Satoshi Sasaki ◽  
Keiko Tanaka ◽  
Wakaba Fukushima ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dietary Intake ◽  
Case Control Study ◽  
Case Control ◽  
B Vitamins ◽  
Vitamin B ◽  
Increased Risk ◽  
The Uk ◽  
Control Study

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case–control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0·87, 0·70 and 0·11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0·56 (0·33, 0·94), 0·69 (0·38, 1·25) and 0·48 (0·23, 0·99), respectively (P for trend = 0·10). In conclusion, in the present case–control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

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