| 1. |
- Alves, Guido, et al.
(författare)
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CSF amyloid-β and tau proteins, and cognitive performance, in early and untreated Parkinson's Disease: the Norwegian ParkWest study
- 2010
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 81:10, s. 1080-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-beta (Abeta) and tau proteins have been found in PDD, with intermediate changes for Abeta42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. Methods CSF concentrations of Abeta42, Abeta40 and Abeta38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. Results PD patients displayed significant reductions in Abeta42 (19%; p=0.009), Abeta40 (15.5%; p=0.008) and Abeta38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Abeta42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Abeta42 (beta=0.205; p=0.019), Abeta40 (beta=0.378; p<0.001) and Abeta38 (beta=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. Conclusion CSF Abeta levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Abeta protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Abeta peptides as prognostic biomarkers in PD.
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| 2. |
- Friedman, Joseph H., et al.
(författare)
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Fatigue Rating Scales Critique and Recommendations by the Movement Disorders Society Task Force on Rating Scales for Parkinson's Disease
- 2010
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 25:7, s. 805-822
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Forskningsöversikt (refereegranskat)abstract
- Fatigue has been shown to be a consistent and common problem in Parkinson's disease (PD) in multiple countries and cultures. It is one of the most disabling of all symptoms, including motor dysfunction, and appears early, often predating the onset of motor symptoms. Several studies of the epidemiology of fatigue have been published, often using different scales, but few on treatment. The Movement Disorder Society (MDS) commissioned a task force to assess available clinical rating scales, critique their psychometric properties, summarize their clinical properties, and evaluate the evidence in support of their use in clinical studies in PD. Six clinical researchers reviewed all studies published in peer reviewed journals of fatigue in PD, evaluated the scales' previous use, performance parameters, and quality of validation data, if available. Scales were rated according to criteria provided by the MDS. A scale was "recommended" if it has been used in clinical studies beyond the group that developed it, has been used in PD and psychometric studies have established that it is a valid, reliable and sensitive to change in people with PD. Requiring a scale to have demonstrated sensitivity to change in PD specifically rather than in other areas in order to attain a rating of "recommended" differs from the use of this term in previous MDS task force scale reviews. "Suggested" scales failed to meet all the criteria of a "recommended" scale, usually the criterion of sensitivity to change in a study of PD. Scales were "listed" if they had been used in PD studies but had little or no psychometric data to assess. Some scales could be used both to screen for fatigue as well as to assess fatigue severity, but some were only used to assess severity. The Fatigue Severity Scale was "recommended" for both screening and severity rating. The Fatigue Assessment Inventory, an expanded version of the Fatigue severity Scale, is "suggested" for both screening and severity. The Functional Assessment of Chronic Illness Therapy-Fatigue was "recommended" for screening and "suggested" for severity. The Multidimensional Fatigue Inventory was "suggested" for screening and "recommended" for severity. The Parkinson Fatigue Scale was "recommended" for screening and "suggested" for severity rating. The Fatigue Severity Inventory was "listed" for both screening and severity. The Fatigue Impact Scale for Daily Use, an adaptation of the Fatigue Impact Scale was "listed" for screening and "suggested" for severity. Visual Analogue and Global Impression Scales are both "listed" for screening and severity. The committee concluded that current scales are adequate for fatigue studies in PD but that studies on sensitivity and specificity of the scales are still needed. (C) 2010 Movement Disorder Society
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| 3. |
- Xu, Xiang Ming, et al.
(författare)
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The Arabidopsis DJ-1a protein confers stress protection through cytosolic SOD activation
- 2010
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 123:10, s. 1644-1651
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the DJ-1 gene (also known as PARK7) cause inherited Parkinson's disease, which is characterized by neuronal death. Although DJ-1 is thought to be an antioxidant protein, the underlying mechanism by which loss of DJ-1 function contributes to cell death is unclear. Human DJ-1 and its Arabidopsis thaliana homologue, AtDJ-1a, are evolutionarily conserved proteins, indicating a universal function. To gain further knowledge of the molecular features associated with DJ-1 dysfunction, we have characterized AtDJ-1a. We show that AtDJ-1a levels are responsive to stress treatment and that AtDJ-1a loss of function results in accelerated cell death in aging plants. By contrast, transgenic plants with elevated AtDJ-1a levels have increased protection against environmental stress conditions, such as strong light, H2O2, methyl viologen and copper sulfate. We further identify superoxide dismutase 1 (SOD1) and glutathione peroxidase 2 (GPX2) as interaction partners of both AtDJ-1a and human DJ-1, and show that this interaction results in AtDJ-1a- and DJ-1-mediated cytosolic SOD1 activation in a copper-dependent fashion. Our data have highlighted a conserved molecular mechanism for DJ-1 and revealed a new protein player in the oxidative stress response of plants.
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