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 possibility of an association between Parkinson's disease and Alzheimer's disease has been examined by studying the age-specific prevalence of Lewy bodies in the substantia nigra in a group of 273 control cases without Parkinson's disease and 121 cases of Alzheimer's disease. The substantia nigra was also studied in 14 cases of Down's syndrome, 13 of which had cortical Alzheimer pathology. Twelve (7.8%) of the controls aged over 60 years showed nigral Lewy bodies. There was mild nerve cell degeneration and/or an extranigral distribution of Lewy bodies, suggestive of presymptomatic Parkinson's disease. Twenty five (22.5%) of the Alzheimer's disease cases over 60 years showed Lewy bodies, but only 14 (14.0%) of these had mild nigral cell loss consistent with presymptomatic Parkinson's disease. No case of Down's syndrome had Lewy bodies. Counts of tangles and plaques in hippocampus, frontal and temporal cortex were lower in cases of Alzheimer's disease with Lewy bodies compared with those without, but cortical choline acetyltransferase (ChAT) activities were similar. This suggests that Lewy body degeneration in the nucleus basalis of Meynert contributes to the deficit of cortical ChAT, but not to the cortical Alzheimer pathology. The relatively small difference in the prevalence of Lewy bodies between controls and Alzheimer's disease could be explained by the additive effects of Lewy body and tangle pathology causing dementia, rather than a greater than chance association between Parkinson's disease and Alzheimer's disease.
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PMID:A pathological study of the association between Lewy body disease and Alzheimer's disease. 254 26

We have evaluated serum alpha 1-antichymotrypsin content in dementia of the Alzheimer type (DAT). The subjects consisted of 26 patients with DAT, 15 with cerebrovascular dementia, 10 with mixed type dementia, 2 with Down syndrome, 17 with Parkinson disease, 14 with spinocerebellar degeneration, 14 with cerebrovascular disease without dementia, 12 with Duchenne muscular dystrophy and 77 normal controls. DAT group showed statistically significant increase of serum alpha 1-antichymotrypsin content, as compared with normal control group (p less than 0.001), mixed type dementia group (p less than 0.05) and other 6 groups (p less than 0.001). However, the levels of both alpha 1-antitrypsin content and inter-alpha-trypsin inhibitor content, included in serine protease inhibitors, were not significantly different between DAT and normal control groups. These findings indicated that measurement of serum alpha 1-antichymotrypsin is useful as the diagnostic marker of DAT.
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PMID:[The significance of measurement of contents of serum serine protease inhibitors in senile dementia of the Alzheimer type]. 260 32

The brains of individuals with dementia due to Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS) exhibit similar neuropathological features, including neuritic plaques, neurofibrillary tangles, and the loss of specific populations of neurons. In addition, these brains show similar transmitter-specific neurochemical alterations. Recent evidence indicates that several pathological and neurochemical changes are related to diseases involving projection systems innervating the telencephalon. At least two transmitter-specific circuits, cholinergic neurons in the basal forebrain and noradrenergic neurons in the locus coeruleus, are selectively affected in many patients with these disorders. This review focuses on these systems because they provide particularly useful examples of the ways in which multidisciplinary studies can provide new clinical-pathological-chemical correlations. Strategies used in these studies are applicable to a wide variety of other neurodegenerative diseases affecting specific populations of neurons. Modern neuropathological approaches to these diseases should eventually allow investigators to directly relate pathogenic processes involving transmitter-specific neuronal populations, whose projections, physiological properties, and functions are known, with the clinical manifestations occurring in human disorders of behavior and cognition.
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PMID:Alzheimer's disease and related dementias: selective involvement of specific neuronal systems. 287 45

The evidence for deficiencies in neurotransmitters in Alzheimer's disease is reviewed. Major losses occur in the subcortical afferent projection systems based on acetylcholine, noradrenaline and serotonin. Within the cortex, somatostatin containing neurones and the large pyramidal cells, presumed to use glutamate/aspartate as transmitters, are the most severely damaged cells. The anatomical distribution of cell loss is explainable if the primary site of damage lies within the cortex; nerve cells are damaged by virtue of their presence within or their connections to this region. The senile plaque may represent the site of this damage and neurofibrillary tangle formation and accumulation may lead to cell death. In patients with Down's syndrome who live past 40 years, changes in transmitters apparently identical to those in Alzheimer's disease occur. The dementia of Parkinson's disease appears related to damage to cholinergic, noradrenergic and dopaminergic systems and may reflect a failure of these subcortical regions to sufficiently "activate" an otherwise undamaged cortex.
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PMID:Neurotransmitter deficits in Alzheimer's disease and in other dementing disorders. 287 73

Ultrastructural study of the nucleus accumbens, caudate nucleus and frontal cortex of patients with Huntington's disease showed that neuronal nuclear membrane indentations were significantly more frequently present in the nucleus accumbens and caudate nucleus, than in a control group. The astrocyte/neuron ratios in the same areas were also found to be higher in the Huntington patients. In a search to find out whether this finding is unique in Huntington's disease the brains of patients with several other diseases of the central nervous system, characterized by involuntary movements and/or dementia (Pick's disease, Down's syndrome, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, tardive dyskinesia and multi-infarct dementia) were investigated in the same way. Although some findings were similar in this group, the Huntingtonian brains could be almost completely separated, with the exception of one patient with Creutzfeldt-Jakob disease, by the use of a discriminant analysis, taking into account the percentage of neurons with nuclear membrane indentation and astrocyte/neuron ratio of three areas of grey matter.
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PMID:Neuronal nuclear membrane indentation and astrocyte/neuron ratio in Huntington's disease. A quantitative electron microscopic study. 293 99

The nucleus basalis of Meynert has been studied extensively in the recent literature. Interest in this nucleus has resulted from the discovery that it is a major source of cortical cholinergic input and that there is neuronal loss in the nucleus basalis in some dementing illnesses. Consistent and severe involvement of the nucleus basalis of Meynert has been found in Alzheimer's disease and in the dementia accompanying Parkinson's disease. Occasional involvement is present in other dementing illnesses, such as progressive supranuclear palsy, Parkinsonism-Dementia complex of Guam, dementia pugilistica, Pick's disease, Korsakoff's syndrome, Down's Syndrome and Creutzfeldt-Jacob disease. Huntington's disease spares this nucleus. However, the role of the nucleus in cognitive function is as yet undetermined. Even its alteration with normal aging remains controversial. This review details the pathological studies of this region to date, with particular emphasis on the dementias. Its role in the dementias of Alzheimer's disease and Parkinson's disease is specifically addressed.
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PMID:The nucleus basalis of Meynert. 293 14

Neurofibrillary tangles occur in a number of apparently distinct neurodegenerative diseases and in normal aging of the human brain. Antibodies raised against Alzheimer's disease paired helical filaments immunolabel the tangles seen in all other tangle-associated disorders examined to date. The neuronal microtubule-associated protein, tau, has recently been identified as an antigenic component of neurofibrillary tangles and senile plaque neurites in Alzheimer's disease. Three different polyclonal antibodies with strong tau immunoreactivity are examined in this study. These antibodies were found to immunostain tangles in normal aged brain and in brains affected by a range of neurodegenerative disorders, including Down's syndrome, Alzheimer's disease plus Parkinson's disease, progressive supranuclear palsy, and the parkinsonism-dementia complex of Guam, as well as Pick bodies in Pick's disease. The findings further illustrate the relative nonspecificity of neurofibrillary lesions in neurodegenerative disorders.
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PMID:Tau antisera recognize neurofibrillary tangles in a range of neurodegenerative disorders. 296 85

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

Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.
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PMID:Cholinergic receptors in cognitive disorders. 379 Oct 66

Neurochemical and histochemical techniques for characterization of neurotransmitters and their receptors in normal and pathological human brain have modified our understanding of Alzheimer's disease. From a hopeless clinico-pathological entity, it has become one of the models of possible physiopathological relations between neurotransmitter anomalies and dementia processes. Three types of neuromediator (or neuro-modulator): cholinergic, aminergic and peptidergic, appear to be affected to different degrees in 5 electively involved anatomical systems: cholinergic innominocorticoamygdalian and septohippocampic systems, noradrenergic ceruleocortical system, serotoninergic pontocortical system and cortical somatostatin and substance P systems. Critical analysis of neurochemical data shows that the biochemical nosology of Alzheimer's disease is confronted by the difficulty of constituting homogeneous series of both normal and pathological cases. Difficulties are increased when an attempt is made to establish correlations between neurotransmitter deficits and lesions or the demential process. This is the result of several factors: individual variability, difficulty in selecting valid controls, time elapsed before post-mortem sampling, imperfect understanding of the progressive topographical course of both cortical and subcortical lesions, which only now are being studied systematically and in a quantifiable manner, and finally the frequent absence of distinction between early and late forms of the disease. Truly senile forms should probably be distinguished, some authors believing them to be a particular type of aging process, from the presenile forms with more extensive biochemical changes. The constant presence of cholinergic symptoms show these to be fundamental features of the dementia but lesions of noradrenergic and serotoninergic systems also probably play an important role, and this triad is found in other dementia processes: trisomy 21, Parkinson's disease with dementia. Numerous questions concerning the neurotransmitter disorders in Alzheimer's disease remain unanswered: to what extent are the lesions due to neurone destruction? What occurs to the receptors? What factors condition severity of the disease? May the latter be directly correlated with the severity of the global dementia process or rather with the constitutive elements of the syndrome such as memory or attention disorders? What are the consequences of the peptidergic lesions? What is the sequential relation between lesions of corticopetal and intracortical afferent systems and what are their respective physiopathological significance?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Neurotransmitter anomalies in Alzheimer's disease]. 615 May 45


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