Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0752347 (Dementia with Lewy bodies)
 1,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 71-year-old man developed signs of progressive dementia, followed by extrapyramidal and motor neuron disease symptoms, which led to death in 6 years. Neuropathological examination revealed neuritic plaques, neurofibrillary tangles, and Lewy bodies in the substantia nigra and neocortex. Atrophy and gliosis with intraneuronal ubiquitin inclusions were present in the anterior horns of the spinal cord. Overlapping of Alzheimer's disease, Parkinson's disease, diffuse Lewy body disease and amyotrophic lateral sclerosis is rare and can increase our understanding of the process of neurodegeneration.
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PMID:Concurrence of Alzheimer's disease, Parkinson's disease, diffuse Lewy body disease, and amyotrophic lateral sclerosis. 773 98

We have previously shown that the brains of patients with Alzheimer's disease (AD) express transforming growth factor (TGF)-beta 2 in neurofibrillary tangle (NFT)-bearing neurons and reactive astrocytes. The present study was undertaken to determine whether other neurodegenerative diseases were also associated with an alteration of the TGF-beta's. The immunohistochemical expression of TGF-beta 1, -2 and -3 was assessed in the brains of patients with progressive supranuclear palsy (n = 2), amyotrophic lateral sclerosis (n = 3), Lewy body disease (n = 5), Parkinson's disease (n = 1), Shy-Drager syndrome (n = 1), Pick's disease (n = 3), lobar atrophy (n = 1), and corticobasal degeneration (n = 2). Our results were compared to norms for controls (n = 8). We found expression of TGF-beta 2 in both NFT bearing neurons and tangle-bearing glial cells in progressive supranuclear palsy and in neurons with age-related NFT formation. Widespread staining of reactive astrocytes for TGF-beta 2 was observed in all degenerative diseases. TGF-beta 1 and -3 staining was not selectively altered in these diseases. We conclude that induction of TGF-beta 2 may be an intrinsic part of the processes that underlie NFT formation and reactive gliosis in a variety of neurodegenerative diseases.
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PMID:Transforming growth factor-beta: neuronal and glial expression in CNS degenerative diseases. 884 36

Before the advent of ubiquitin immunochemistry and immunogold electron microscopy, there was no known intracellular molecular commonality between neurodegenerative diseases. The application of antibodies which primarily detect ubiquitin protein conjugates has shown that all of the human and animal idiopathic and transmissible chronic neurodegenerative diseases, (including Alzheimer's disease (AD), Lewy body disease (LBD), amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD) and scrapie) are related by some form of intraneuronal inclusion which contains ubiquitin protein conjugates. In addition, disorders such as Alzheimer's disease, CJD and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins which may be associated with cytoskeletal reorganisation. Although our knowledge about these diseases is increasing, they remain largely untreatable. Recently, attention has focused on the mechanisms of production of different types of amyloid and the likely involvement within cells of the endosome-lysosome system, organelles which are immuno-positive for ubiquitin protein conjugates. These organelles may be 'bioreactor' sites for the unfolding and partial degradation of membrane proteins to generate the amyloid materials or their precursors which subsequently become expelled from the cell, or are released from dead cells, and accumulate as pathological entities. Such common features of the disease processes give new direction to therapeutic intervention.
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PMID:Endosome-lysosomes, ubiquitin and neurodegeneration. 886 Oct 20

We report a 72-year-old man with sporadic amyotrophic lateral sclerosis (ALS) who showed concomitant histopathology of Alzheimer's disease (AD) and incidental Lewy body disease. The patient presented at the age of 70 years with distal upper limb amyotrophy. Thereafter, gait disturbance and respiratory distress progressed. Neuropathological examination showed mild frontal lobe and anterior spinal root atrophy. There was moderate loss of upper and lower motor neurons, and Bunina bodies and skein-like inclusions were present in the spinal anterior horns and facial and hypoglossal nuclei, confirming the pathology of ALS. In addition, however, numerous amyloid plaques were observed throughout the entire cerebral neocortex, nucleus accumbens and amygdaloid body. Many neurofibrillary tangles were also evident in the medial temporal cortex. Moreover, the substantia nigra showed mild degeneration, and Lewy bodies were found in the substantia nigra, locus ceruleus, basal nucleus of Meynert and peripheral autonomic ganglia. Although neither parkinsonism nor dementia was noted during the clinical course, our final neuropathological diagnosis was sporadic ALS, AD and incidental Lewy body disease (or presymptomatic Parkinson's disease). Whether or not the coexistence of these three diseases in the same patient was merely coincidental is of considerable interest.
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PMID:[An autopsy case of amyotrophic lateral sclerosis with concomitant Alzheimer's and incidental Lewy body diseases]. 892 32

In susceptible species, aluminum induces cytoskeletal changes in which neurofilaments accumulate in neuronal cell bodies and proximal axonal enlargements. To determine if microtubule-associated proteins (MAPs) are altered in this model, we examined the spinal cords of aluminum- and saline-treated control rabbits at several time points after treatment. Transient decreases in tau and MAP2 immunoreactivity in neurons in aluminum-intoxicated rabbits were demonstrated with immunocytochemistry. An antibody directed against Alzheimer's disease paired helical filaments labeled neurons in aluminum-treated rabbits but not controls. MAP5 immunoreactivity in the cell body cytoplasm was displaced by aluminum-induced tangles. The transient decreases in MAP2 and tau immunoreactivity did not reflect alterations in protein levels measured using immunoblotting. The transient antigenic changes in tau and MAP2 may reflect conformational changes in these cytoskeletal proteins. Aluminum-induced pathology provides a model for studying perturbations in MAPs and neurofilament proteins that are characteristic of many human neurodegenerative diseases such as Alzheimer's disease, diffuse Lewy body disease, Parkinson's disease, and amyotrophic lateral sclerosis.
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PMID:Aluminum-induced neuropathology: transient changes in microtubule-associated proteins. 894 45

Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2'-deoxyguanosine (OH8dG) levels were increased in SALS motor cortex but not in FALS patients. Malondialdehyde levels showed no significant changes. Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehyde-modified protein, and OH8dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS.
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PMID:Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. 934 52

Apoptosis is likely to be an important mechanism of cell loss in neurodegenerative diseases, but the signaling cascades activated before DNA fragmentation have not yet been determined. p53 or CD95 gene up-regulation precedes apoptosis in many cell types, and a potential role for these molecules in apoptosis of neurons and glial cells has already been demonstrated in Alzheimer's disease (AD). To determine whether apoptosis in other neurodegenerative diseases is mediated by similar mechanisms, p53 and CD95 expression were examined in postmortem central nervous system tissues from patients with diffuse Lewy body disease (DLBD), Pick's disease (PkD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Down's syndrome plus Alzheimer's disease (DN+AD). Quantitative immunoblot analysis demonstrated higher temporal lobe levels of p53 and CD95 proteins in DLBD, PkD, and DN+AD, and higher temporal lobe levels of CD95 only in MSA and PSP relative to PD and aged controls (for all, p < 0.01). In histologic sections, increased p53 immunoreactivity was localized in neuronal and glial cell nuclei, neuronal perikarya, and dystrophic neuritic and glial cell processes in the frontal (Area 1 1) and temporal (Area 21) lobes in DLBD, PkD, and DN+AD, the motor cortex and spinal ventral horns in ALS, and the striatum and midbrain in DLBD, MSA, PD, and PSP. Increased CD95 expression and nuclear DNA fragmentation were present in the same cell types and structures that manifested increased nuclear p53 immunoreactivity. The results suggest that p53- or CD95-associated apoptosis may be a common mechanism of cell loss in several important neurodegenerative diseases. In addition, the presence of abundant p53-immunoreactive neurites and glial cell processes appears to be a novel feature of neurodegeneration shared by these distinct diseases.
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PMID:P53- and CD95-associated apoptosis in neurodegenerative diseases. 956 85

Autosomal dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Previous studies have implicated the involvement of metabolic dysfunction in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined SOD activity and mitochondrial oxidative phosphorylation enzyme activities in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Cytosolic SOD activity, predominantly Cu/Zn SOD, was decreased approximately 50% in all regions in FALS patients with SOD mutations but was not significantly altered in other patient groups. Marked increases in complex I and II-III activities were seen in FALS patients with SOD mutations but not in SALS patients. We also measured electron transport chain enzyme activities in a transgenic mouse model of FALS. Complex I activity was significantly increased in the forebrain of 60-day-old G93A transgenic mice overexpressing human mutant SOD1, relative to levels in transgenic wild-type animals, supporting the hypothesis that the motor neuron disorder associated with SOD1 mutations involves a defect in mitochondrial energy metabolism.
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PMID:Metabolic dysfunction in familial, but not sporadic, amyotrophic lateral sclerosis. 964 76

Cytoplasmic RNA species have been identified recently within neurofibrillary tangles and senile plaques of Alzheimer's disease brain. To determine whether RNA sequestration is a common feature of other lesions found in progressive neurodegenerative disorders, acridine orange histofluorescence was employed, alone or in combination with immunohistochemistry and thioflavine-S staining to identify RNA species in paraffin-embedded brain tissue sections. Postmortem samples came from 39 subjects with the following diagnoses: Alzheimer's disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, corticobasal degeneration, diffuse Lewy body disease, normal controls, multiple system atrophy, Parkinson's disease, Pick's disease, progressive supranuclear palsy, and Shy-Drager syndrome. RNAs were detected in neurofibrillary tangles and neuritic senile plaques as well as in Pick bodies. However, Lewy bodies, Hirano bodies, and cytoplasmic glial inclusions did not contain abundant cytoplasmic RNA species. These observations demonstrate the selective localization of RNA species to distinct pathological lesions of neurodegenerative disease brains.
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PMID:RNA sequestration to pathological lesions of neurodegenerative diseases. 982 12

Neuronal loss, synaptic disconnection and neuritic sprouting correlate with dementia in Alzheimer's disease (AD). Nitric oxide (NO) is an important synaptic plasticity molecule generated by nitric oxide synthase (NOS) oxidation of a guanidino nitrogen of L-arginine. Experimentally, the NOS III gene is modulated with neuritic sprouting. In a previous study, NOS III expression was found to be abnormal in cortical neurons, white matter glial cells, and dystrophic neurites in AD and Down syndrome brains. The present study demonstrates the same abnormalities in neuronal and glial NOS III expression with massive proliferation of NOS III-immunoreactive neurites and glial cell processes in other neurodegenerative diseases including: diffuse Lewy body disease, Pick's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, multiple system atrophy, and Parkinson's disease. However, each disease, including AD, was distinguished by the selective alterations in NOS III expression and sprouting in structures marred by neurodegeneration. Double label immunohistochemical staining studies demonstrated nitrotyrosine and NOS III co-localized in only rare neurons and neuritic sprouts, suggesting that peroxynitrite formation and nitration of growth cone proteins may not be important consequences of NOS III enzyme accumulation. The results suggest that aberrant NOS III expression and NOS III-associated neuritic sprouting in the CNS are major abnormalities common to several important neurodegenerative diseases.
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PMID:Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases. 1020 79


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