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 population of neurons situated in the human cerebral neocortex contains mRNA coding for tyrosine hydroxylase, the key enzyme for catecholamine biosynthesis. Phosphorylated neurofilament-containing cytoplasmic inclusions occur in these neurons in diffuse Lewy body disease, indicating a tendency for selective involvement that is shared with subcortical catecholamine-containing neurons. These findings are relevant to the pathophysiology of several neurologic and psychiatric illnesses in which the monoamine-containing neurons of the neocortex may participate.
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PMID:Lewy bodies in tyrosine hydroxylase-synthesizing neurons of the human cerebral cortex. 257 69

Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocytochemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.
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PMID:Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. 791 27

Three cases of Lewy body disease were investigated in order to compare the morphological and immunohistochemical characteristics of the neuronal inclusions in the cerebral cortex (CC) and brain-stem (BS). Ultrastructurally, the CC contained intermediate-sized filaments with variable amounts of granular material and other organelles, whereas the BS consisted of an electron-dense core and an outer area with radially oriented filaments. The cerebral cortex was immuno-reactive with antibodies against tyrosine hydroxylase (TH) and tau protein, and differed from BS. In addition, although the CC were antigenically similar to BS in their neurofilament (70, 160 and 200 kDa) and ubiquitin contents, the localization of neurofilament immunoreactivity differed between them, being confined positively to the core of CC, but to the periphery of the BS. Although Lewy bodies (LB) in idiopathic Parkinson's disease are morphologically similar to BS, they have been reported to differ in their immunoreactivity with antibodies against tau. It has been reported that CC differ from LB with regard to immunoreactivity with antibodies against TH and tropomyosin. It is inferred that these inclusions (CC, BS and LB) differ in morphogenesis.
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PMID:Immunohistochemistry of neuronal inclusions in the cerebral cortex and brain-stem in Lewy body disease. 829 42

Argyrophilic glial inclusions, which are immunohistochemically positive for alpha-synuclein but negative for tau protein, were examined in the brain of Parkinson's disease (PD) patients. Autopsied brains of 10 individuals who died from PD, of two incidental Lewy body disease cases and of five age-matched individuals whose deaths were caused by non-neurological diseases were studied, histopathologically, by Gallyas-Braak staining and, immunohistochemically, with anti-alpha-synuclein antibody, anti-ubiquitin, and anti-tyrosine hydroxylase. All postmortem PD brains showed a significant number of argyrophilic glial inclusions, but no glial inclusions were found in control brains. The inclusions were found not only in the regions showing neuronal loss and gliosis, such as the substantia nigra, locus ceruleus and dorsal vagal nucleus, but also in regions without neuronal loss and gliosis, such as the cerebral cortex, cerebral white matter, striatum, globus pallidus, thalamus, cerebellum and spinal cord. The distribution and density of glial inclusions in PD brains varied from case to case but, in the cerebral cortex, the number of glial inclusions were fairly well correlated with the number of Lewy bodies. The distribution pattern of glial inclusions also showed a striking resemblance to that of catecholaminergic neurones and fibres. The abnormal accumulation of alpha-synuclein in glial cells was more widespread than neurone loss, and appears to be an important pathological feature of PD.
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PMID:Widespread occurrence of argyrophilic glial inclusions in Parkinson's disease. 1167 88

We sought to determine the involvement of medullary regions controlling sympathetic output in pathologically confirmed diffuse Lewy body disease (LBD). We studied eight limbic or neocortical stage LBD and eight multiple system atrophy (MSA) cases, confirmed neuropathologically, and eight age-matched controls. Five of the LBD cases and all MSA cases had orthostatic hypotension. Serial 50-mum sections obtained from the medulla rostral to the obex were immunostained for tyrosine hydroxylase, tryptophan hydroxylase and alpha-synuclein. Analysis was focused on the ventrolateral medulla and medullary raphe nuclei. In LBD cases, there were Lewy bodies and neurites, as well as dystrophic neurons in the ventrolateral medulla, but the number of catecholaminergic and serotonergic neurons was not significantly reduced. All these groups were depleted in MSA. There were Lewy body pathology and dystrophic neurons in the raphe in all LBD cases. Cell numbers were reduced in both the raphe obscurus and raphe pallidus. Our findings suggest that, although LBD affects medullary autonomic areas, it does so less severely than MSA, particularly in the case of the VLM, which controls sympathetic outputs maintaining arterial pressure. In LBD, orthostatic hypotension may be due primarily to involvement of sympathetic ganglion neurons rather than ventrolateral medulla neurons.
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PMID:Involvement of medullary regions controlling sympathetic output in Lewy body disease. 1563 29

We performed [123I]-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in 180 patients with PD, 24 patients with DLB and 73 patients with the other related diseases. The heart-to-mediastinum (H/M) ratio in PD and DLB was significantly low compared to that in MSA, PSP, CBD and AD. The H/M ratio tended to decrease with the disease progression in PD. These findings suggest that MIBG myocardial scintigraphy could be a marker for differential diagnosis of PD and DLB. We immunohistochemically examined heart tissues from patients with pathologically confirmed PD, DLB and the other related diseases using monoclonal antibody against tyrosine hydroxylase (TH). The number of TH-immunoreactive nerve fibers in the epicardium was moderate or abundant in most patients with MSA, PSP, CBD and AD as well as in the control subjects. Contrarily, the number of TH-immunoreactive nerve fibers in the epicardium had almost completely disappeared in nearly all the patients with PD and DLB. These findings suggest that postganglionic cardiac sympathetic nerve denervation occurs in PD and DLB but not in MSA, PSP, CBD and AD, which accounts for the decreased cardiac uptake of MIBG in PD and DLB, but not in the other diseases.
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PMID:[A useful marker for differential diagnosis of Parkinson's disease--MIBG myocardial scintigraphy]. 1565 4

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer's disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antibody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.
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PMID:Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. 1593 69

We investigated whether the cytokines produced in activated microglia in the substantia nigra (SN) and putamen in sporadic Parkinson's disease (PD) are neuroprotective or neurotoxic. In autopsy brains of PD, the number of MHC class II (CR3/43)-positive activated microglia, which were also ICAM-1 (CD 54)-, LFA-1 (CD 11a)-, TNF-alpha-, and IL-6-positive, increased in the SN and putamen during progress of PD. At the early stage activated microglia were mainly associated with tyrosine hydroxylase (TH)-positive neurites in the putamen, and at the advanced stage with damaged TH-positive neurons in the SN. The activated microglia in PD were observed not only in the nigro-striatal region, but also in various brain regions such as the hippocampus and cerebral cortex. We examined the distribution of activated microglia and the expression of cytokines and neurotrophins in the hippocampus of PD and Lewy body disease (LBD). The levels of IL-6 and TNF-alpha mRNAs increased both in PD and LBD, but those of BDNF mRNA and protein drastically decreased specifically in LBD, in which neuronal loss was observed not only in the nigro-striatum but also in the hippocampus. The results suggest activated microglia in the hippocampus to be probably neuroprotective in PD, but those to be neurotoxic in LBD. As an evidence supporting this hypothesis, two subsets of microglia were isolated from mouse brain by cell sorting: one subset with high production of reactive oxygen species (ROS) and the other with no production of ROS. When co-cultured with neuronal cells, one microglia clone with high ROS production was neurotoxic, but another clone with no ROS production neuroprotective. On the other hand, Sawada with coworkers found that a neuroprotective microglial clone in a culture experiment converted to a toxic microglial clone by transduction of the HIV-1 Nef protein with increasing NADPH oxidase activity. Taken together, all these results suggest that activated microglia may change in vivo from neuroprotective to neurotoxic subtsets as degeneration of dopamine neurons in the SN progresses in PD. We conclude that the cytokines from activated microglia in the SN and putamen may be initially neuroprotective, but may later become neurotoxic during the progress of PD. Toxic change of activated microglia may also occur in Alzheimer's disease and other neurodegenerative diseases in which inflammatory process is found.
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PMID:Role of cytokines in inflammatory process in Parkinson's disease. 1701 56

Lewy bodies (LB) usually extend from the brainstem to the cerebrum in patients with Parkinson's disease. However, whether the patterns of progression of LB and neuronal loss in Parkinson's disease are identical to those in other Lewy body diseases (LBD) remains unclear. In addition, pathological data on the autonomic nervous system involvement in LBD are limited. We present here the clinicopathological characteristics of two autopsy cases with both Alzheimer's disease and dementia with Lewy bodies (DLB), possibly diagnosed as having Lewy body variant of Alzheimer's disease (LBV/AD). Our patients presented clinically with dementia without parkinsonism. Histopathologically, phosphorylated alpha-synuclein-positive LB and Lewy neurites were abundant in the limbic system, especially in the amygdala, and to a lesser degree, in the neocortex, including the primary motor cortex. The amygdala was also most severely affected by neuronal loss, and the other limbic areas and neocortex were affected to a lesser degree. Despite the existence of a small number of LB and many Lewy neurites, neurons in the brainstem nuclei were relatively well preserved. The Braak stages of concurrent neurofibrillary changes and senile plaques were stage V and C, respectively, in both cases. Tyrosine hydroxylase-positive nerve fibers were relatively well spared in one case examined compared with Parkinson's disease cases. Furthermore, many Lewy neurites immunopositive for phosphorylated a-synuclein were found in the nerve fascicles of the epicardium in one case examined and in Parkinson's disease cases to a lesser degree. These findings suggest that: (i) in at least some LBV/AD cases, the amygdala develops neuronal loss and Lewy-related pathology prior to the brainstem nuclei; and (ii) the depletion of nerves in the heart tissue of LBV/AD is not necessarily complete despite the development of Lewy-related pathology.
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PMID:Lewy body variant of Alzheimer's disease or cerebral type lewy body disease? Two autopsy cases of presenile onset with minimal involvement of the brainstem. 1731 80

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Parkinsonism in DLB is mainly caused by neuronal loss with Lewy bodies (LBs) in the substantia nigra, thereby inducing degeneration of the nigrostriatal dopaminergic pathway similar to that in Parkinson's disease (PD). To clarify the pathogenesis of DLB, it is important to investigate the mechanisms involved in the degenerative process of LB-bearing neurones. Several reports suggest a role for nuclear factor kappa-B (NFkappaB) in the manifestation of neurodegenerative conditions such as AD and PD. The aim of the present study was to investigate whether NFkappaB subunits are involved in the pathogenesis of neurodegeneration in DLB by measuring tyrosine hydroxylase (TH), NFkappaB p65 and p50 protein expression in frontal cortex and substantia nigra pars compacta of DLB and control human brains. An increase, although not statistically significant, in nigral TH expression in DLB cases was observed. There were no differences in the cortical and nigral expression levels of NFkappaB p65 subunit between control and DLB cases. Western blots of the frontal cortex showed no differences in the expression levels of NFkappaB p50 subunit. However, NFkappaB p50 levels were significantly decreased (P < 0.05) in the pars compacta of the substantia nigra in the DLB cases in comparison with controls. The decrease in the expression of the p50 subunit in the substantia nigra of DLB cases achieved in the present study may increase the vulnerability of the dopaminergic neurones to a possible neurotoxic effect of p65 subunit. Thus, normal levels of NFkappaB p65 might be toxic in neurones with a low expression of the NFkappaB p50 subunit.
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PMID:Nuclear factor kappa-B p50 and p65 subunits expression in dementia with Lewy bodies. 1744 64


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