Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.
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PMID:Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan. 1854

The prevalence of cerebral amyloid angiopathy (CAA) and its association with intellectual decline in idiopathic Parkinson's disease (iPD) remain unclear. To identify the role of CAA in iPD dementia the prevalence and severity of CAA were investigated, with particular respect to changes in vessel wall structure. Twenty-eight autopsy Parkinsonian brains and fourteen age-matched controls, post-mortem revised histopathologically for the presence of alpha-synuclein and Alzheimer's disease (AD)-type pathology, using standardized clinico-neuropathological criteria, underwent further investigation. Histological, immunohistochemical staining methods with antibodies to amyloid beta-peptide, alpha-actin, collagen III, collagen IV and CD34 as well as ultrastructural methods were used. The findings showed that the prevalence of CAA in the iPD cohort was higher (53%) than in controls (28%). CAA occurred more frequently in the iPD+AD (70%) sub-set than in the iPD-AD (44%) one. The progression of CAA was differentiated, with predominance of mild stage. Diminished smooth muscle actin and collagen IV expression in the vascular media with concomitant collagen III positive immunoreactivity in the intima were observed only in very severe CAA. Ultrastructural assay revealed degenerative changes in vessel smooth muscle cells and thickening of their basement membrane with the focal accumulation of amyloid fibres and fibrillar collagen in both iPD -AD and iPD+AD cases, but the most severe CAA-type changes were visible in the iPD+AD sub-set. The same type of immunoreactivity (Abeta42 positive and Abeta40 positive) of arterial CAA and parenchymal neuritic plaques, as well as capillary CAA and diffuse plaques (Abeta42 positive and Abeta40 negative), may indicate pathogenic similarities and differences between both types of degenerative changes on the one hand and time-different changes or local different processing of amyloid precursor protein on the other.
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PMID:Amyloid angiopathy in idiopathic Parkinson's disease. Immunohistochemical and ultrastructural study. 1916 67

We tested the hypothesis that vibratory thresholds in the elderly are related to mobility. In all, 629 older persons without dementia underwent testing including 11 lower extremity performance measures and modified United Parkinson's Disease Rating Scale (UPDRS), summarized as composite mobility and global parkinsonian signs. Vibratory thresholds were measured at the ankle and toes bilaterally using the graduated Rydel-Seiffer tuning fork. In linear regression models adjusted for age, sex, and education, vibratory threshold was associated with composite mobility (estimate, 0.047, SE = 0.011, P < 0.001) and global parkinsonian signs score (estimate, -0.252, SE = 0.126, P = 0.047). These findings were primarily due to the association of vibratory threshold with gait and balance components of composite mobility and parkinsonian gait. These results were unchanged when we controlled for body mass index, physical activity, cognition, depression, vascular risk factors, vascular disease burden, joint pain, and falls. Vibratory thresholds are associated with mobility, supporting the link between peripheral sensory nerve function and mobility in the elderly.
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PMID:Vibratory thresholds and mobility in older persons. 1930 25

The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n=16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an "innocent-bystander". The entire role of the LB in PD dementia is again brought into question.
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PMID:Parkinson's disease dementia: a diminished role for the Lewy body. 1934 54

We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.
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PMID:A clinico-pathological study of subtypes in Parkinson's disease. 1975 3

The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal-and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.
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PMID:Possible treatment concepts for the levodopa-related hyperhomocysteinemia. 2002 36

Eating and swallowing disorders are developed in various periods of feeding. Aspiration, one eating disorder, induces aspiration pneumonitis. Elderly people have higher rate of mortality from aspiration pneumonitis. It is important that aspiration is relate to the breathing mechanism. Both swallowing and breathing are regulated by a solitary tract and aspects of the central nerve system. Eating and swallowing disorders develop as an aftereffect of central nerve system damage (e.g., minimal cerebral vascular disease or Parkinson's disease). Swallowing is regulated by the vagus nerve and glossophayngeal nerve via secretion of substance P, and the amount of substance P secretion depends on the content of dopamine in the basal nucleus. Therefore, dopamine supplement drugs (e.g., L-dopa or amantadine hydrochloride), and agents to block substance P degradation (e.g., angiotensin-converting enzyme) are effective in the treatment of eating disorders. Thus, these indicate that we require an understanding of neuropsychopharmacology for the development of new medical treatments for eating and swallowing disorders.
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PMID:[Eating disorders and central nervous system damage]. 2003 Jan 88

Human paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that exhibits a broad substrate specificity. In addition to protecting against exposure to some organophosphorus (OP) pesticides by hydrolyzing their toxic oxon metabolites, PON1 is important in protecting against vascular disease by metabolizing oxidized lipids. Recently, PON1 has also been shown to play a role in inactivating the quorum sensing factor N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL) of Pseudomonas aeruginosa. Native, untagged engineered recombinant human PON1 (rHuPON1) expressed in Escherichia coli and purified by conventional column chromatographic purification is stable, active, and capable of protecting PON1 knockout mice (PON1(-/-)) from exposure to high levels of the OP compound diazoxon. The bacterially derived rHuPON1 can be produced in large quantities and lacks the glycosylation of eukaryotic systems that can produce immunogenic complications when inappropriately glycosylated recombinant proteins are used as therapeutics. Previous studies have shown that the determination of PON1 status, which reveals both PON1(192) functional genotype and serum enzyme activity level, is required for a meaningful evaluation of PON1's role in risk of disease or exposure. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates, allowing for use of this protocol in non-specialized laboratories. Factors were also determined for inter-converting rates of hydrolysis of different substrates. PON1 status also plays an important role in revealing changes in HDL-associated PON1 activities in male patients with Parkinson disease (PD). Immunolocalization studies of PONs 1, 2 and 3 in nearly all mouse tissues suggest that the functions of PONs 1 and 3 extend beyond the plasma and the HDL particle.
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PMID:Human PON1, a biomarker of risk of disease and exposure. 2033 54

Cerebrovascular pathology is a major cause of stroke and mortality. Studies on prevalence of cerebrovascular pathologies in dementia with Lewy bodies (DLBs) and Parkinson disease (PD) patients are scarce and contradictory. We aimed to determine the prevalence and severity of cerebrovascular pathologies in DLB and PD and to analyze their relationship to LB pathology. The prevalence and severity of atherosclerosis in the circle of Willis, cerebral amyloid angiopathy, cerebral infarcts, hemorrhages, small-vessel disease, white matter lesions, including the Consortium to Establish a Registry for Alzheimer Disease (CERAD) protocol as well as Braak neurofibrillary tangle stages for AD pathology were analyzed in autopsy-verified DLB (n = 13), PD (n = 102), and control subjects (n = 53). In all patient groups, the extent of LB pathology was inversely correlated to the severity of most vascular pathologies (atherosclerosis, infarcts, and small-vessel disease; all p < 0.05). By contrast, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were positively correlated with LB pathology (p < 0.05). Whereas the overall prevalence and severity of small-vessel disease, infarcts, hemorrhages, and white matter lesions were comparable among both disease groups, the extents of atherosclerosis, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were significantly higher in DLB than in those of PD patients (p < 0.05). Microinfarcts were statistically more prevalent in each patient group than in controls, whereas gross infarcts predominated in controls (p < 0.05 each). In conclusion, DLB and PD patients with advanced LB pathology were less likely to show severe cerebrovascular disease or history of stroke.
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PMID:Inverse relationship between cerebrovascular lesions and severity of lewy body pathology in patients with lewy body diseases. 2041 82

Cerebro-vascular disease is a well-known cause of parkinsonism. However, so far, there are no standardized clinical criteria that allow the diagnosis with accuracy and reliability. Rather, there is a great symptom overlap between idiopathic Parkinson's disease, other causes for parkinsonism, and vascular parkinsonism. Therefore, additional instruments are necessary to improve diagnostic accuracy. Transcranial sonography of brain parenchyma (TCS) has become a broadly applied tool in the diagnosis of Parkinson's disease, and secondary and atypical parkinsonian syndromes. In contrast to patients with idiopathic Parkinson's disease, patients with vascular parkinsonism in general show no hyperechogenicity of the substantia nigra. In contrast to a number of patients with atypical parkinsonian syndromes, also the basal ganglia are usually normoechogenic on TCS. A more specific approach to vascular parkinsonism includes the Doppler or duplex technique in order to show stenosis of vessels. Therefore, the combination of TCS and Doppler/duplex imaging might help to improve diagnosis of vascular parkinsonism transcranial.
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PMID:Transcranial sonography in the discrimination of Parkinson's disease versus vascular parkinsonism. 2069 99


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