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)

The nature of Lewy bodies (LBs) in the brain stem and cerebral cortex in five cases of diffuse Lewy body disease and one case of Parkinson's disease with dementia were investigated immunocytochemically with various antibodies to cytoskeletal proteins, paired helical filaments (PHF) and ubiquitin. Antibodies to 200-kDa component of neurofilament, tau and PHF showed no significant reactions with most of LBs. Antibodies to high-molecular weight microtubule-associated proteins (HMWMAPs) moderately stained the periphery of a few of LBs. A monoclonal antibody to PHF (DF2) which recognizes ubiquitin, and polyclonal antibodies to ubiquitin immunostained virtually all of the typical and cortical LBs as intensely as Alzheimer's neurofibrillary tangles and senile plaque neurites: the periphery of LBs was darkly stained, whereas the central core of typical LBs and central zone of cortical LBs were less intensely stained or remained unstained. Immunoelectron microscopy of the LBs with DF2 revealed that immune reaction products were located on the filaments exclusively in the periphery of LBs, but not on those in the center. These findings suggest that both types of LBs are immunocytochemically indistinguishable despite some structural differences, and that peripherally located filaments in LBs are tagged with ubiquitin, an element required for the ATP-dependent proteolysis system in the cell. Antibodies to ubiquitin are the most useful marker of LBs ever known.
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PMID:Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. 336 59

We have examined the pathological basis for dementia in elderly patients with Lewy-type Parkinson's disease (PD). 37 (66.1%) of 56 examined cases (mean age of 77.9 years) had evidence of dementia. According to the distribution pattern of Lewy bodies and senile changes, as well as abiotrophic changes of the nucleus basalis of Meynert, nucleus paranigralis and locus ceruleus, demented PD could be subdivided into three groups: (1) demented PD without cerebral alzheimerization (21.6%, 8 cases); (2) demented PD with cerebral alzheimerization (64.9%, 24 cases), and (3) demented PD with combined senile-vascular changes (13.5%). Based on neuropathological findings, damage not to a single, but to multiple neuronal networks including the innominatocortical cholinergic, ceruleocortical noradrenergic as well as mesocortical dopaminergic systems could play a role in the development of dementia in PD. We also discussed the nosological situation of 'diffuse Lewy body disease', regarding it as one distinct disease entity.
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PMID:Pathological basis for dementia in elderly patients with idiopathic Parkinson's disease. 337 59

The term Lewy body disease (LBD) was proposed earlier to describe a disease classified into three types (A, B, and C) according to the distributional pattern of Lewy bodies in the CNS. Group A (diffuse type of LBD) shows clinical symptoms of "dementia-parkinsonism syndrome". The most remarkable pathologic feature is the widespread appearance of numerous Lewy bodies not only in the brain stem and diencephalon (as in group C), but also in the cerebral cortex and basal ganglia, which is complicated by senile changes of various degrees. Group B is the transitional type between groups A and C. Group C (brain stem type of LBD) is identical with idiopathic Parkinson's disease. In this paper, 12 of our cases with diffuse type LBD were studied clinicopathologically and compared with eight similar cases in the literature. The neuropathologic substrate of progressive dementia in this disease is also discussed. LBD is a clinicopathologic entity; the diffuse type of LBD, a special form of this disease, presents mainly a presenile dementia.
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PMID:Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree--a new disease? 609 67

The immunoreactivity of cortical and brainstem-type Lewy bodies has been investigates with antibodies to the cyclin-dependent kinase 5 (cdk5), to the extracellular regulated kinase 1 (ERK-1), and to the cdc2p34 kinase and with antibodies specific for phosphorylation epitopes typical of paired helical filament-tau (PHF-tau). Both cortical and brainstem-type Lewy bodies in diffuse Lewy body disease and brainstem-type Lewy bodies in Parkinson's disease were found to be immunoreactive for cdk5 but not for cdc2p34 or ERK-1 or with the PHF-tau antibodies. Double immunolabeling showed that cdk5-positive Lewy bodies were also ubiquitin immunoreactive and that cdk5 antibodies labeled as many Lewy bodies as ubiquitin antibodies in adequately fixed tissue. The cdk5 immunoreactivity of Lewy bodies was abolished by preabsorption of the antibody with a cdk5 peptide. The antibodies to cdk5 labeled a single 33-kd species on Western blots of human brain homogenates, with a similar intensity in control, diffuse Lewy body disease, and Alzheimer's disease, and this cdk5 species was found mainly in the particulate fraction of brain homogenates. This observation suggests that cdk5 might be a protein kinase involved in the phosphorylation of a molecular component of Lewy bodies, for example, neurofilament proteins known to be present in these inclusions.
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PMID:Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. 748 9

Community pathologists are often called on to perform autopsies to confirm clinical diagnoses of Alzheimer's disease, by far the most common cause of dementia. Diagnostic criteria have been provided by the Consortium to Establish a Registry for Alzheimer's Disease. Beyond pure and simple Alzheimer's disease, a significant proportion of dementia brains will feature Alzheimer's disease mixed with Lewy bodies, historically associated with idiopathic Parkinson's disease, or combined with various manifestations of cerebrovascular disease. Less commonly, the pathologist will encounter Lewy body disease alone, pure cerebrovascular disease, Pick's disease, progressive supranuclear palsy, Creutzfeldt-Jakob disease, or dementia lacking distinctive histopathology. This article is intended to reacquaint pathologists with these disorders and to provide a practical step-by-step approach to making the diagnosis of these mixed and non-Alzheimer's dementias.
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PMID:Making the diagnosis of mixed and non-Alzheimer's dementias. 748 2

Recent evidence, based upon immunocytochemical and histochemical analysis of brain cortical tissue from alzheimer's disease patients, has suggested that altered activity and/or distribution of the lysosomal proteases cathepsins B and D may be implicated in the abnormal protein processing pathway resulting in formation of the neurotoxic amyloid A4 peptide, characteristic of this neurodegenerative disorder. We have therefore compared, via biochemical assay techniques using conventional or specially synthesised (corresponding to protein cleavage points of relevant to A4 peptide formation) fluorogenic substrates, the levels of activity of the lysosomal proteases cathepsins B, D, H and L, and dipeptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from control and Alzheimer's disease patients. For comparative purposes, activity levels of the above enzymes were also determined in frontal cortex tissue from cases with Lewy body dementia and Parkinson's disease, and in caudate tissue from control and Huntington's disease cases. There was no significant difference in activity for any protease types in tissue from control cases and cases with Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the exception of reduced dipeptidyl aminopeptidase II activity in Lewy body dementia and Parkinson's cases. We have therefore been unable to confirm a potential role for lysosomal cathepsins in the characteristic neurodegeneration associated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases with Huntington's disease is of particular note. We therefore suggest the potential role of the latter enzymes in the pathogenesis of Huntington's disease requires further investigation.
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PMID:Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease. 756 49

An anti-tau monoclonal antibody tau-2 was demonstrated to react with the cells which characteristically appeared in the subcortical nuclei of certain neurodegenerative disorders. These cells had rod-like cell bodies and elongated processes, whose morphology was consistent with that of reactive microglia (tau-2 positive microglia-like cells; TPMC). TPMC were diffusely scattered in the subcortical nuclei, especially the putamen, irrelevant to focal tissue injury such as infarcts and amyloid deposits. TPMC were positively immunostained with anti-ferritin antibody, but negatively with LN3, anti-GFAP, other kinds of anti-tau and anti-neurofilament antibodies. TPMC were found in some cases of Alzheimer type dementia and diffuse Lewy body disease, but not in the cases of Parkinson's disease, Pick's disease and control without neurological disorder. Similar microglia-like cells were found around infarctic foci and amyloid cores of senile plaques, regardless of the disorder. They were, however, different from TPMC in that they were positively immunostained with LN3.
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PMID:Investigation of tau-2 positive microglia-like cells in the subcortical nuclei of human neurodegenerative disorders. 756 36

GAP-43 is a growth-associated phosphoprotein expressed at high levels in neurons during development, axonal regeneration, and neuritic sprouting. GAP-43 gene expression in mature neurons is probably functionally important for the structural remodeling of synapses as required for learning and establishing new memory. The widespread aberrant neuritic growth accompanied by impaired synaptic plasticity in Alzheimer's disease (AD) suggests that abnormal GAP-43 gene expression may contribute to the cascade of neurodegeneration. In the present study, end-stage AD brains exhibited reduced neuronal expression but increased glial cell levels of GAP-43 mRNA and protein. Glial cell localization of GAP-43 gene expression was confirmed by in situ hybridization of cerebral tissue, Northern blot analysis of microdissected cerebral white matter, and independent analysis of astrocytoma cell lines and primary malignant astrocytomas. In addition, in AD, GAP-43 immunoreactivity was translocated from the cytosol to membranes of swollen neuritic (dendritic) and glial cell processes throughout cerebral cortex and white matter. Downregulated and aberrant neuronal GAP-43 gene expression appears to reflect an important molecular lesion that precedes and progresses with the widespread synaptic disconnection and dementia in AD. At the same time, the presence of similar neuronal abnormalities in Pick's disease, diffuse Lewy body disease, Parkinson's disease, and Down syndrome suggests common mechanisms in the respective cascades of neurodegeneration. Finally, the finding of aberrantly increased glial cell GAP-43 gene expression in AD exposes a previously unrecognized neurodegenerative change that may account for the axonal loss and white matter atrophy detected early in the course of disease.
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PMID:Aberrant GAP-43 gene expression in Alzheimer's disease. 757 69

We report of 51-year-old man with early onset parkinsonism. The patient was well until 38 years of age, when he noted a difficulty in the use of his right leg; this difficulty improved after he received a medicine from his physician. He did not take medicine regularly, and he noted difficulty in standing up from a chair and in rolling over at age 40. Tremor was not a feature, but he noted slowness in his movements at age 42; at age 49, he noted diurnal fluctuation in his symptoms and at times he experienced hallucination. He was admitted to our hospital in September of 1992 for the first time when he was 50-year-old. At that time, neurologic examination revealed an alert and somewhat bradyphrenic man; Hasegawa dementia rating scale was 20/30. Cranial nerves were intact except for masked face and small voice. He showed stooped posture and small step gait cogwheel rigidity was noted in the four limbs more on the left; tremor was absent. Deep reflexes were within normal range and the sensation was intact. As he showed diurnal fluctuation in his symptoms, his medication was switched to levodopa 3,000 mg/day without a peripheral decarboxylase inhibitor. He was discharged for out patient follow up. But he did not take drugs regularly, and his neurologic condition deteriorated; he was admitted to another hospital. Neurologic examination at that time was essentially similar to that of his first admission to our hospital, except that he showed more severe rigidity and akinesia; again tremor was not detected. His cranial CT scan showed a mild ventricular dilatation without cortical or brain stem atrophy. During his hospital stay, he developed episodes of oculogyric crisis during peak dose of levodopa, and orthostatic hypotension. He developed pneumonia and expired on October 28, 1993. He was discussed in a neurological CPC, and the chief discussion arrived at the conclusion that the patient had early onset Parkinson's disease of Lewy body type. As differential diagnoses, early onset parkinsonism without Lewy body, pure form of diffuse Lewy body disease, pallidoluysian atrophy, and other conditions were considered; however, all of those possibilities were excluded. Early onset parkinsonism without Lewy body would have much earlier onset than this patient, and diffuse Lewy body disease would show more profound dementia 13 years after the onset. Pallidoluysian atrophy would be complicated with some dystonic features. Post-mortem examination showed marked discoloration and degeneration of the substantia nigra. The degeneration was most prominent in the ventrolateral tier of the substantia nigra.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A 51-year-old man with early onset parkinsonism]. 760 92

Thirty patients with dementia defined by DSM-III-R criteria (Alzheimer's disease (22), vascular dementia (3), Parkinson's disease, frontal lobe dementia, possible diffuse Lewy body dementia, normal pressure hydrocephalus and uncertain diagnosis), with scores below 24 points in the Mini-Mental Status Examination and more than 4 years of education were submitted to a neuropsychological evaluation. The scores in the neuropsychological tests were compared to those obtained by thirty normal volunteers paired for age, sex and education. Sensitivity, specificity and accuracy of the tests in the distinction of demented and normal volunteers were determined. The accuracies were calculated using ROC curves. Blessed's information-memory-concentration test showed greatest accuracy, followed by copy of simple figures, delayed memory of 10 figures (after 5 minutes), recognition of 10 figures and verbal fluency test (animals). A linear discriminant function, composed by 6 tests: visual perception, incidental memory, delayed memory (after 5 minutes), drawing of a clock, verbal fluency (animals) and calculation tests, was able to discriminate all controls from patients and only one patient was wrongly classified as normal control. These tests were chosen because they can be applied in less than 10 minutes and are very easy to interpret. This discriminant function must be applied in another group of patients and controls in order to demonstrate its value. When associated to the MMSE it may be useful to discriminate patients with dementia from normal people in epidemiological studies.
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PMID:[Neuropsychological tests of simple application for diagnosing dementia]. 761 36


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