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

Silver techniques for intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) and extracellular A4-amyloid deposits were used to examine lesions of the cerebral cortex in six cases of progressive supranuclear palsy (three were mentally unimpaired and three showed moderate degrees of dementia). Deposits of A4-amyloid protein occurred in small numbers or were absent. Neurofibrillary tangles and neuropil threads were present in all cases and were largely confined to the allocortex. A characteristic pattern of changes was found in the entorhinal cortex. The three mentally unimpaired individuals had mild cortical changes virtually confined to the transentorhinal region while all of the demented patients showed severe destruction of the superficial cellular layer in both the transentorhinal and entorhinal region. This pattern of allocortical destruction closely resembles that seen in clinically incipient Alzheimer's disease or in mentally impaired cases of Parkinson's disease. The entorhinal region receives dense input from isocortical association areas and projects via the perforant path to the hippocampal formation. The cells of origin of major portions of the perforant path are located within the superficial entorhinal cellular layer. Destruction of this layer partially or totally disconnects the hippocampus from the isocortex. The specific pattern of entorhinal destruction is considered to contribute to cognitive impairment and personality changes, frequently seen in patients with progressive supranuclear palsy.
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PMID:Allocortical neurofibrillary changes in progressive supranuclear palsy. 146 62

Alz-50 is a monoclonal antibody that immunoreacts with neurofibrillary tangles and neurites in brains with Alzheimer's disease (AD). In addition, the levels of Alz-50 immunoreactivity in brain, measured by either enzyme-linked immunosorbent assay or ALZ-enzyme-linked immunosorbant assay (EIA), are increased in AD relative to age-matched controls. The current study compares the distribution and extent of Alz-50 immunostaining with quantified levels of Alz-50 immunoreactivity measured in adjacent frozen blocks of tissue by ALZ-EIA. The brain tissue studied was obtained from individuals with AD, AD + Down's syndrome (AD + DN), Parkinson's disease with dementia (PD), or AD + PD, and from nondemented aged controls. In AD, AD + DN, and AD + PD, there were significantly higher densities of Alz-50-immunoreactive (AFI) neurons, more abundant diffuse AFI neurites, and higher ALZ-EIA values than in aged controls. In PD, the overall mean density of AFI neurons was significantly lower than in AD and AD + DN, but AFI neurites were as abundant as they were in brains with an AD diagnosis. However, PD was readily distinguished from AD and AD + DN by significantly lower mean ALZ-EIA values, and significantly lower densities of neurofilament-immuno-reactive AD lesions. Multiple-regression analysis demonstrated significant correlations between ALZ-EIA levels and the severity of AD lesions, and the density of AFI neurites, but not with the density of AFI neurons. Therefore, ALZ-EIA levels may represent only a portion of the Alz-50 immunoreactivity detectable by immunohistochemical staining.
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PMID:Immunohistochemical and histopathologic correlates of Alzheimer's disease-associated Alz-50 immunoreactivity quantified in homogenates of cerebral tissue. 146 3

Subsumed under the rubric of Lewy body disease are idiopathic Parkinson's disease (PD), pure diffuse Lewy body disease (DLBD), and, most commonly, combined brainstem and neocortical Lewy bodies with Alzheimer's disease (AD) pathology in a relatively early developmental stage. Clinical correlates are dementia with psychiatric and subcortical features plus mild extrapyramidal signs (EPS).
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PMID:Lewy body disease. 146 83

Neuronal thread protein is a recently characterized, approximately 20-kd protein that accumulates in brains with Alzheimer's disease (AD) lesions. This study examined whether concentrations of neuronal thread protein (NTP) were also increased in the cerebrospinal fluid (CSF) of individuals with probable (clinically diagnosed) and definite (histopathologically proved) AD. Using a highly sensitive three-site monoclonal antibody-based immunoradiometric assay, we measured NTP concentrations in CSF from 84 patients with probable AD and mild dementia (duration, 4.05 +/- 0.36 years), 45 with Parkinson's disease and minimal or no dementia (duration, 4.73 +/- 0.78 years), 73 with multiple sclerosis, and 73 nondemented control subjects. NTP concentrations were also measured in postmortem ventricular fluid and temporal lobe neocortex extracts from 31 subjects with histopathologically proved AD and 14 age-matched control subjects. The mean concentration of NTP in the CSF was higher in AD (4.15 +/- 0.25 ng/ml; 95% confidence interval [CI] limits, 3.65-4.65) than in Parkinson's disease (1.96 +/- 0.16 ng/ml; 95% CI, 1.65-2.27), multiple sclerosis (1.6 +/- 0.14 ng/ml; 95% CI limits, 1.33-1.88), or control subjects (1.27 +/- 0.06 ng/ml; 95% CI limits, 1.15-1.40) (p < 0.001). In addition, 70% of the patients with probable AD had concentrations of NTP in CSF that were higher than 2.5 ng/ml (> upper 99% CI limit in the control group), compared with 23% of Parkinson's disease patients, 11% of multiple sclerosis patients, and 4% of control subjects. The mean concentrations of NTP in the ventricular fluid and brain tissue from individuals with documented AD and end-stage dementia were threefold higher than the levels detected in the CSF from the remaining patients with probable AD and mild dementia. Moreover, of 9 patients with AD, postmortem brain and CSF manifested 5- to 50-fold higher levels of NTP compared with the CSF samples obtained an average of 6 years earlier. These findings demonstrate that NTP levels are elevated in the CSF of individuals with AD and that NTP levels in the CSF increase strikingly with progression of dementia and neuronal degeneration.
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PMID:Increased levels of neuronal thread protein in cerebrospinal fluid of patients with Alzheimer's disease. 147 63

The hypothalamus sensu stricto consists of the chiasmatic, the tuberal and the mamillary region. The present study is confined to the poorly myelinated chiasmatic and tuberal region. Both regions harbor many nuclear grays with relatively clear-cut boundaries embedded in an ill-defined nerve cell assembly referred to as the hypothalamic gray. Prominent components of the chiasmatic region are the magnocellular neurosecretory complex (supraoptic nucleus, paraventricular nucleus, accessory neurosecretory nucleus), the sexually dimorphic intermediate nucleus, the suprachiasmatic and retrochiasmatic nuclei. The dominating structure of the tuberal region is the complex of the ventromedial, posteromedial and dorsomedial nuclei supplemented by the periventricular and infundibular nuclei. Lateral portions of the tuber cinereum harbor the lateral tuberal nucleus and the tuberomamillary nucleus. The lateral tuberal nucleus exhibits pronounced cell loss in Huntington's chorea and is also severely involved in cases of dementia with argyrophilic grains. The large nerve cells of the tuberomamillary nucleus show particularly severe affection in both Alzheimer's (intraneuronal neurofibrillary changes) and Parkinson's disease (Lewy bodies).
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PMID:Anatomy of the human hypothalamus (chiasmatic and tuberal region). 148 Jul 54

Neuronal thread protein (NTP) is a recently characterized molecule that is over-expressed in brains with Alzheimer's disease (AD) lesions. The present study encompasses a detailed analysis of NTP expression in AD compared with other neurodegenerative diseases and aged controls. Using a specific monoclonal antibody, NTP immunoreactivity was evaluated in 309 paraffin-embedded sections from 8 different regions of the frontal, parietal, and temporal lobes of 73 brains with AD, AD + Down's syndrome (DN), AD + Parkinson's disease (PD), PD dementia (PDD), aged controls, and disease controls with Huntington's disease, multi-infarct dementia, or schizophrenia. In 250 adjacent blocks of snap-frozen unfixed tissue the concentration of NTP (ng/mg of protein) was measured using a 3-site forward sandwich monoclonal antibody based immunoradiometric assay (M-IRMA). Immunohistochemical studies demonstrated that brains with AD, AD + PD, and AD + DN contained significantly higher densities of NTP immunoreactive neurons and more frequent immunostaining of neuropil and white matter fibers compared with PDD and aged controls (both P < 0.001) which had few or no AD lesions. In addition, the overall mean concentrations of NTP in AD, AD + PD, and AD + DN were significantly higher than in PDD and aged controls (P < 0.005). Greater degrees of NTP immunoreactivity and higher concentrations of the protein in cerebral tissue were significantly correlated with AD diagnosis and abundant neurofibrillary tangles (P < 0.005). The findings suggest that NTP over-expression may serve as a marker for the type of neuronal degeneration that occurs in AD.
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PMID:Neuronal thread protein over-expression in brains with Alzheimer's disease lesions. 148 53

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinson's disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinson's patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinson's disease is similar to that seen in Alzheimer's disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinson's disease may be similar to that in Alzheimer's disease.
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PMID:Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease. 149 39

Recent studies have shown that compensatory processes have an important role in counteracting the neurodegenerative changes underlining Alzheimer's disease (AD), much like their well known role in Parkinson's disease (PD). In the light of these reports, we review the findings of the positive correlation existing between the appearance of extra-pyramidal symptoms and an increased rate of progression in AD patients. We propose that this correlated symptomatology arises from the wasting of globally shared compensatory resources, manifested both in an increasing inability to compensate for persisting sub-clinical nigral lesions, and in enhanced AD deterioration rate. Our hypothesis gains support from various clinical reports and by the neural modeling of synaptic changes in AD.
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PMID:Extra-pyramidal symptoms in Alzheimer's disease: a hypothesis. 149 18

Using energy-dispersive x-ray analysis on an electron microscope working in the scanning transmission electron microscopy mode equipped with a microanalysis system, we studied the subcellular distribution of trace elements in neuromelanin-containing neurons of the substantia nigra zona compacta (SNZC) of three cases of idiopathic Parkinson's disease (PD) [one with Alzheimer's disease (AD)] and of three controls, in Lewy bodies of SNZC, and in synthetic dopamine-melanin chemically charged or uncharged with Fe. Weak but significant Fe peaks similar to those of a synthetic melanin-Fe3+ complex were seen only in intraneuronal highly electron-dense neuromelanin granules of SNZC cells of PD brains, with the highest levels in a case of PD plus AD, whereas a synthetic melanin-Fe2+ complex showed much lower iron peaks, indicating that neuromelanin has higher affinity for Fe3+ than for Fe2+. No detectable Fe was seen in nonmelanized cytoplasm of SNZC neurons and in the adjacent neuropil in both PD and controls, in Lewy bodies in SNZC neurons in PD, and in synthetic dopamine-melanin uncharged with iron. These findings, demonstrating for the first time a neuromelanin-iron complex in dopaminergic SNZC neurons in PD, support the assumption that an iron-melanin interaction contributes significantly to dopaminergic neurodegeneration in PD and PD plus AD.
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PMID:Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. 149 4

(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, the activity of which significantly increases with age. (-)Deprenyl was the first selective inhibitor of MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type MAO, and is still the only MAO-B inhibitor in clinical use. (b) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine and is presently the only safe MAO inhibitor which can be administered without dietary restrictions. (c) Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. (d) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the MAO or the uptake inhibitory effects of the drug. All in all, (-)deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline-treated peers. Parkinsonians on levodopa plus (-)deprenyl (10 mg daily) lived significantly longer than those on levodopa alone. (-)Deprenyl is the first drug which retards the progress of Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)deprenyl did not require levodopa until significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improved the performance of patients with Alzheimer's disease. It is concluded that in Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacological basis of the therapeutic effect of (-)deprenyl in age-related neurological diseases. 151 86


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