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)

Choline acetyltransferase (ChAT) activity, the sedimentation and solubility forms of acetylcholinesterase (AChE) as well as total (3H-quinuclidinyl benzilate, QNB) and M1 (3H-pirenzepine, PZ) muscarinic binding were investigated in the temporal cortex (TC) and nucleus caudatus (NC) of both non-demented and demented parkinsonian patients and controls. ChAT activity and low-salt-soluble and detergent-soluble AChE were lower in the TC of demented patients with Parkinson's disease than in controls. ChAT activity and the solubility forms of AChE in the NC did not differ between controls and parkinsonian patients. In the TC, the activity of the intermediate form of AChE was lower in parkinsonian patients, but the activity of the light form of AChE did not differ between controls and parkinsonian patients. In the TC of patients with Parkinson's disease the Bmax of 3H-QNB binding was slightly higher than in controls, but the Bmax of 3H-PZ binding did not differ between controls and parkinsonian patients. In the NC the Bmax of 3H-QNB binding was unchanged compared to that of the controls. The concomitant decrease of ChAT with soluble as well as membrane-bound tetrameric AChE suggests a close relationship between ChAT and tetrameric form of AChE. M1 receptors (3H-PZ binding sites) are not affected in the TC, but are decreased in the NC of demented parkinsonian patients. This decrease may be secondary to the loss of dopaminergic neurons projecting from the substantia nigra to the striatum.
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PMID:Different forms of brain acetylcholinesterase and muscarinic binding in Parkinson's disease. 272 71

Acetylcholinesterase (AChE) activity was measured in cerebrospinal fluid (CSF) from 25 patients with senile dementia of Alzheimer type (SDAT), 11 patients with vascular dementia (VD), 26 patients with Parkinson's disease (PD), and 30 normal controls. AChE activity also was measured in 46 normal subjects whose ages ranged from 15 to 85 to evaluate the effect of age on AChE activity. CSF AChE activity for the SDAT, VD and PD groups showed no significant difference compared with the value for the control group. However, there were significant decreases in CSF AChE activity in the VD and PD groups with the development of ventricular enlargement. There was no significant correlation between CSF AChE activity decrease and ventricular enlargement in the SDAT group. AChE activity increased significantly over the age range of 15 to 85. These results suggest that, although CSF AChE activity is not a useful parameter in the diagnosis of dementia, it may be a marker indicating abnormalities of the intracerebral cholinergic system during the process of cerebral atrophy.
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PMID:[Acetylcholinesterase activity in CSF in senile dementia of Alzheimer type, vascular dementia, and Parkinson's disease]. 275 67

Mean levels of the two hydrolases angiotensin-converting enzyme (ACE) and acetylcholinesterase (AChE), the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and total protein concentration were examined in cerebrospinal fluid (CSF) samples from a group of patients with dementia of the Alzheimer's type, a group of comparably demented patients with Parkinson's disease, and a neurologically healthy elderly control group. Both pathological groups exhibited a significant decrease in the mean levels of ACE activity and DOPAC per milliliter and were distinguishable from one another based on mean CSH HVA levels. Unlike the Parkinson's disease group, whose mean concentration of HVA was lower than, but not significantly different from that of the control group, the mean HVA concentration of the Alzheimer's disease group was significantly elevated. In contrast, comparisons of the mean CSF AChE activity (expressed per milliliter or per milligram of protein) and CSF total protein concentration did not reveal significant differences for any of the groups. Independent of CSF protein concentration, ACE activity per milliliter exhibited a positive correlation with AChE activity per milliliter within the control and Parkinson's disease groups, whereas a statistically significant correlation for these CSF hydrolases was not observed within the Alzheimer's disease group. Thus, the CSF profiles for patients with mild dementias associated with Alzheimer's or Parkinson's disease differed by at least two neurochemical criteria. Based on the levels of ACE activity, DOPAC, and HVA per milliliter of CSF, two discriminant functions were derived and resulted in the correct classification of 71% of all subjects (n = 38) into Alzheimer's disease, Parkinson's disease, and neurologically healthy control groups.
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PMID:Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study. 302 46

The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less severe change (-37%) in the hippocampus. The magnitude of the enzyme reduction in cerebral cortex was equal to or greater than that reported in brain of demented Alzheimer's and Parkinson's disease patients having loss of AChE-containing nucleus basalis cholinergic neurons. It is concluded that the data provide additional biochemical evidence suggesting a cerebral cortical cholinergic denervation in OPCA.
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PMID:Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy. 316 41

The cholinergic neurons located within the pedunculopontine nucleus (Ch5) of patients with Alzheimer's disease (AD; n = 15), Parkinson's disease (PD; n = 2), and neurologically normal (n = 6) subjects were visualized immunohistochemically using choline acetyltransferase, pharmacohistochemically using acetylcholinesterase, or by reduced histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Each histochemical procedure localized a well-delineated, compact lateral group and a more diffuse medial group of neurons within the pedunculopontine nucleus. Co-localization experiments revealed that all three enzymes marked the same population of cholinergic neurons. The extent of pathological alterations associated with the cholinergic neurons within the compact lateral sector of the pedunculopontine nucleus was examined in sections that reacted for NADPH-d, counterstained with thioflavin-S. The average number of neurofibrillary tangles within this portion of the pedunculopontine nucleus was 25.4 (range 0-70) in patients with AD, 1.5 (range 1-2) in those with PD, and 1.2 (range 0-4) in aged control subjects. Of the total number of neurofibrillary tangles counted in AD cases, 72.7% were end-stage ghosts and 27.3% were tangle-bearing neurons. The pathological alteration of cholinergic neurons of the compact lateral aspect of the pedunculopontine nucleus may play a role in some of the behavioral features characteristic of AD.
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PMID:Neurofibrillary tangles in cholinergic pedunculopontine neurons in Alzheimer's disease. 320 15

Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease.
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PMID:Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. 333 58

In this study we investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities and the molecular forms of these enzymes in the cerebrospinal fluid (CSF) of non-demented and demented Parkinsonian patients and in controls. The ratio of AChE to BChE activity was lower in the CSF of demented patients than in non-demented patients, although AChE and BChE activities and the molecular forms of AChE and BChE were the same in the different groups of patients. AChE activity in CSF did not vary according to the severity or duration of dementia associated with Parkinson's disease or with the disability stage of Parkinson's disease. BChE activity in CSF correlated with these clinical parameters, and patients with cerebral atrophy had higher BChE activity in CSF than those patients without atrophy. These alterations in the BChE activity of CSF may be related to gliosis which occurs in the degenerating brain tissue.
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PMID:Acetyl- and butyrylcholinesterase activity in the cerebrospinal fluid of patients with Parkinson's disease. 369 32

The molecular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were studied in frontal cortex (grey and white matter), postmortem, and in cerebrospinal fluid (CSF) of demented patients with Parkinson's disease compared to controls and non-demented parkinsonians. In the frontal cortex, AChE activity decreased significantly in both demented and non-demented parkinsonian subjects compared to controls; the 10S form of the enzyme was significantly lower in demented parkinsonians than in the non-demented subjects. The decrease in AChE activity was correlated with a decrease in choline acetyltransferase activity thought to reflect lesion of cholinergic neurones in the substantia innominata which innervate the cerebral cortex. BChE activity decreased only in the non-demented parkinsonians; in the demented subjects, BChE activity was at control levels. Similar results were obtained with grey and white matter, although absolute levels of the two enzymes were different in the two types of tissue, suggesting that the enzymes were affected in the cholinergic neurones before transport to cortical nerve terminals. No decreases in AChE or BChE activity were observed in the CSF of the patients studied. On the contrary, AChE and BChE levels were significantly higher in demented parkinsonian patients compared to the non-demented subjects.
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PMID:Acetylcholinesterase and butyrylcholinesterase in frontal cortex and cerebrospinal fluid of demented and non-demented patients with Parkinson's disease. 394 70

Dementia in Parkinson's disease has previously been attributed to the presence in the cerebral cortex of Alzheimer-type neuropathological abnormalities. New evidence suggests, however, that dementia in this disease usually occurs in the absence of substantial Alzheimer-type changes in the cortex and may be related to abnormalities in the cortical cholinergic system. Thus, in Parkinsonian patients with dementia there were extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline acetyltransferase reductions in temporal neocortex correlated with the degree of mental impairment assessed by a test of memory and information but not with the extent of plaque or tangle formation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly temporal) choline acetyltransferase correlated with the number of neurons in the nucleus of Meynert suggesting that primary degeneration of these cholinergic neurons may be related, directly or indirectly, to declining cognitive function in Parkinson's disease.
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PMID:Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease. 399 51

We examined the relationship of disease laterality to neuropsychological and neurochemical features in patients with idiopathic Parkinson's disease (PD). We tested patients with PD, patients with Alzheimer's type of senile dementia, and a control group neuropsychologically, and we determined their CSF levels of homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindolacetic acid, serotonin, and acetylcholinesterase. The patients with PD were divided into two groups depending on the side of the body with greater disease involvement. Both parkinsonian groups, those more affected on the left (group L) and those more affected on the right (group R), were otherwise similar in all other clinical and historical features. Group L patients showed greater neuropsychological impairments than group R patients. Group L also had significantly higher CSF levels of homovanillic acid and acetylcholinesterase than group R. These findings of neuropsychological and neurochemical differences between groups L and R suggest functional or anatomic asymmetries of dopaminergic systems in the CNS.
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PMID:Parkinson's disease. The possible relationship of laterality to dementia and neurochemical findings. 647 29


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