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)

It has been suggested that dystrophic neurites in the hippocampal CA2-3 sector are characteristic of diffuse Lewy body disease (DLBD) but not of Parkinson's disease (PD). We investigated the severity of neuritic change in the CA2-3 sector of the hippocampus and in the periamygdaloid cortex (PAC) in 45 patients with clinically diagnosed and neuropathologically verified PD. Samples from amygdala, hippocampus, entorhinal cortex (ERC) and cortical gyri were examined for Alzheimer-type (AD) changes and Lewy bodies (LBs) using antibodies against ubiquitin and tau. Ubiquitin-positive but polyclonal tau-negative neurites were detected in the CA2-3 region of the hippocampus in 88% of patients and in the PAC in 91% of patients. The CA2-3 sector neurites correlated significantly only with LBs in all other brain areas, except in the amygdala. The neurites in the PAC correlated significantly with neuropathological variables in all other brain areas examined, except with tangles in the pre-central and frontal gyrus and with LBs in the amygdala and in the ERC. Unlike in the CA2-3 sector, the neuritic change in the PAC was more prominent in those PD patients with more severe cognitive impairment (P = 0.03). There was no significant correlation between the apoE4 allele load and the neuritic change in the PAC or in the CA2-3 sector. Our study revealed that cortical LBs and neuritic change in the amygdala and hippocampal CA2-3 sector co-exist in PD. Unlike hippocampal neurites, the PAC neurites are related to AD pathology. There seems to be a relationship between the PAC neurites and cognitive impairment in PD, but its significance needs further elucidation.
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PMID:Neuritic degeneration in the hippocampus and amygdala in Parkinson's disease in relation to Alzheimer pathology. 1044 55

Pathogenic alpha-synuclein (alphaS) gene mutations occur in rare familial Parkinson's disease (PD) kindreds, and wild-type alphaS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease, but beta-synuclein (betaS) and gamma-synuclein (gammaS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to alphaS and betaS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to gammaS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the alphaS- and betaS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative "synucleinopathies" by implicating betaS and gammaS, in addition to alphaS, in the onset/progression of PD and DLB.
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PMID:Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein. 1055 41

Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are distinguishable clinically but often not neuropathologically. This study aims to test whether the distribution of cortical Lewy bodies differs in these clinicopathological groups and to develop diagnostic protocols for their differentiation. Brains were obtained at autopsy from cases recruited from prospective clinical studies of dementia or movement disorders. All cases with significant pathologies other than Lewy bodies or plaques were excluded. Cases were categorised into either PD without dementia, DLB (dementia first or within 2 years of disease onset), or PD with a later onset of dementia (PDD). The distribution and density of Lewy bodies and Lewy neurites was determined using antibodies to ubiquitin and alpha-synuclein. Cortical Lewy body densities could not separate cases of DLB from those with PDD. However, semiquantitative thresholds in the parahippocampus could separate demented from non-demented cases with high sensitivity and specificity. Interactions between multiple pathologies were determined using factor analysis. Although many cases had CA2 Lewy neurites, this was not associated with severity or duration of either dementia or parkinsonism. Most DLB cases had significant plaque pathology, and severity and duration of dementia was related to both increasing parahippocampal Lewy body densities and neuritic plaque grade. Weighted kappa statistics revealed that the combination of these pathologies indicated a more severe dementia. These results suggest that dual pathologies cause DLB, and high densities of parahippocampal Lewy bodies indicate dementia regardless of additional pathologies.
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PMID:Cortical Lewy body pathology in the diagnosis of dementia. 1160 11

Diffuse neurofibrillary tangles with calcification (DNTC) is a rare tangle-predominant dementia, as well as one of the tauopathies lacking Abeta deposition. It is characterized by temporo-frontal lobar atrophy, Fahr-type calcification and, histopathologically, numerous neurofibrillary tangles in the limbic system and neocortex. Recently, accumulation of alpha-synuclein (alphaS), the precursor of the non-beta amyloid component (NAC) of Alzheimer's disease, has been shown in diverse neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, multiple system atrophy and parkinsonism-dementia complex of Guam. To clarify whether alphaS accumulates in other neurodegenerative disorders, we investigated eight DNTC brains using immunohistochemistry and demonstrated remarkable alphaS deposition in the neurons and astrocytes in many anatomical regions. Abundant Lewy bodies were observed in the amygdala (seven cases) and hippocampus (seven cases), and, to a lesser degree, in the substantia nigra (six cases) and dorsal vagal nucleus (five cases). In the hippocampus, many Lewy neurites were distributed in the stratum oriens and stratum pyramidale in the CA2-3 and the subiculum. Furthermore, numerous NAC-positive astrocytes were detected in the hippocampus and temporal cortex. This investigation reveals that neurons and astrocytes are extensively involved in remarkable alphaS pathology in the DNTC brain, and that the alphaS pathology compounds the cardinal pathological features of tau pathology. These findings suggest that (1) DNTC shares a common pathophysiological background with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy in which abnormal alphaS aggregation is observed, and (2) there is an interaction between alphaS and tau pathology that does not involve amyloid in DNTC.
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PMID:NACP/alpha-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC). 1220 Jun 18

The present study concerns an autopsied case of dementia with Lewy bodies (DLB) showing advanced Lewy pathology but minimal Alzheimer pathology. The patient was a 50-year-old Japanese male without inheritance. His initial symptoms at the age of 43 suggested the diagnosis ofjuvenile idiopathic Parkinson's disease (PD), but were followed by memory disturbance 1 year later. He showed parkinsonism, dementia, personality change, fluctuating cognition and visual hallucinations 3 years later. Neuroradiological examination revealed moderate brain atrophy, predominantly in the frontal and temporal lobes. Neuropathological examination demonstrated a widespread occurrence of Lewy bodies (LB) with LB-related neurites not only in the brainstem but also in the cerebrum. The present case showed Lewy pathology which corresponded to stage IV by our staging and was parallel to neuronal loss. There was marked neuronal loss with many LB-related neurites in the CA2 of the hippocampus. Neurofibrillary tangles (NFT) were almost restricted to the entorhinal cortex, while senile plaques were absent. Consequently, the present case was pathologically diagnosed as having DLB of the neocortical type, pure form. In the present study, we suggest that Lewy pathology in the cerebral cortex could be responsible for progressive dementia.
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PMID:Dementia with Lewy bodies showing advanced Lewy pathology but minimal Alzheimer pathology--Lewy pathology causes neuronal loss inducing progressive dementia. 1248 76

The understanding of the molecular mechanisms underlying Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy has made significant progress in the recent years. Lewy body appears to be principally made of alpha-synuclein, a presynaptic protein. It also contains ubiquitin and some components of the proteasome: this suggests that alteration of protein catabolism may be involved in its formation. In favor of this hypothesis, it should be noted that Parkin, a protein that is mutated in autosomal recessive Parkinson disease, is a ubiquitin ligase. Immunohistochemistry has shown that alpha-synuclein accumulates not only in the cell body of the neurones (Lewy body) but also in their processes (Lewy neurites); it has emphasized the severity of the pathology in the nucleus basalis of Meynert, amygdala, CA2-3 sector of the hippocampus and cerebral cortex. Cortical Lewy bodies are not considered any more the marker of dementia with Lewy bodies: they are, indeed, found in true Parkinson disease cases. In progressive supranuclear palsy, 4 repeats tau accumulates in the cytoplasm of neurones and glia. At electron microscopy, the accumulation is made of straight filaments. It involves not only the neurones (where it is the main constituent of the neurofibrillary tangles) but also the glia. Astrocytic tuft is to day considered the morphological marker of progressive supranuclear palsy. Tau protein accumulates in the cell body of the oligodendrocyte as a "coiled body"; the protein is also integrated in the myelin sheath, when the cytoplasm of the oligodendrocyte wraps around the axon. This explains the numerous "threads" that are visible in cases of progressive supranuclear palsy. Striato-nigral degeneration, sporadic olivo-ponto-cerebellar atrophy and primitive orthostatic hypotension are various clinico-pathologic aspects of the same disorder: multiple system atrophy. It is also characterized by a morphological marker: the accumulation of alpha-synuclein in the cytoplasm of glial cells, particularly oligodendrocytes. The term synucleinopathy has been proposed to describe both idiopathic Parkinson disease and multiple system atrophy. The reason explaining the cellular topography of alpha-synuclein accumulation, neuronal in Parkinson disease, glial in multiple system atrophy is still unknown.
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PMID:[Recent neuropathology of parkinsonian syndromes]. 1277 83

The morphological background of cognitive and emotional impairments in Parkinson's disease (PD) has not yet been fully explained. We evaluated the expression of synaptic proteins: alpha- and beta-synuclein, synaptophysin and synaptobrevin and ultrastructural changes of perikaryons and axons in limbic structures at post-mortem from cases of PD to estimate degenerative axonal pathology in the hippocampus and amygdala [corrected]. Limbic structures (enthorinal cortex, hippocampus, and amygdala) are essential for the cognitive processes and emotional behaviour. We found that presynaptic axon pathology is mostly connected with hippocampal CA2-3 and dentate hilar regions as well as with the cortical and medio-central complexes of amygdala. Heterogeneous immunoreactivity of alpha-synuclein and diversified ultrastructure of Lewy bodies (LBs) and Lewy neurites (LNs) indicate their consecutive developmental stages. We observed an excessive perineuroneal expression of synaptophysin in the dentate hilar region in all PD cases, except one. This suggests that the dysfunction of synapses in this region may result from axonal pathology. Our study indicates a relation between cognitive and behavioural symptomatology in PD and alpha-synuclein dependent axonal pathology in the hippocampus and amygdala.
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PMID:Degenerative axonal changes in the hippocampus and amygdala in Parkinson's disease. 1497 49

The present study is an attempt to reclassify the pathological subtypes of DLB based on both Lewy pathology and Alzheimer pathology, and to clarify the pathological boundary between DLB and Parkinson's disease (PD) or Alzheimer's disease (AD) in autopsied cases, using pathological and immunohistochemical methods. Dementia with Lewy bodies was classified into the limbic type and neocortical type according to the degree of Lewy pathology, including Lewy bodies (LB) and LB-related neurites, by our staging and was classified into the pure form, common form and AD form according to the degree of Alzheimer pathology including NFT and amyloid deposits by Braak staging. These combined subtypes were lined up on a spectrum not only with Lewy pathology but also with other DLB-related pathologies including Alzheimer pathology, neuronal loss in the substantia nigra, spongiform change in the transentorhinal cortex and LB-related neurites in the CA2-3 region. There were some similarities in both Lewy pathology and other DLB-related pathologies between PD and DLB, although Lewy pathology of PD was below the lowest stage of Lewy pathology. In contrast, AD did not meet the stages of Lewy pathology, and there were also no similarities in other DLB-related pathologies between AD and DLB. In addition, LB of AD showed the characteristics different from those of DLB on the coexistence of LB with NFT. These present findings suggest that DLB has pathological continuity with PD, but can be pathologically differentiated from AD. The present study clarified the pathological entity of DLB, compared with PD and AD.
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PMID:Dementia with Lewy bodies: reclassification of pathological subtypes and boundary with Parkinson's disease or Alzheimer's disease. 1506 76

To better understand the pathogenesis of brain dysfunction in Gaucher disease (GD), we studied brain pathology in seven subjects with type 1 GD (four also exhibited parkinsonism and dementia), three with type 2 GD and four with type 3 GD. Unique pathologic patterns of disease involving the hippocampal CA2-4 regions and layer 4b of the calcarine cortex were identified. While these findings were common to all three GD phenotypes, the extent of the changes varied depending on the severity of disease. Cerebral cortical layers 3 and 5, hippocampal CA2-4, and layer 4b were involved in all GD patients. Neuronal loss predominated in both type 2 and type 3 patients with progressive myoclonic encephalopathy, whereas patients classified as type 1 GD had only astrogliosis. Adjacent regions and lamina, including hippocampal CA1 and calcarine lamina 4a and 4c were spared of pathology, highlighting the specificity of the vulnerability of selective neurons. Elevated glucocerebrosidase expression by immunohistochemistry was found in CA2-4. Hippocampal (45)Ca(2+) uptake autoradiography in rat brain was performed demonstrating that hippocampal CA2-4 neurons, rather than CA1 neurons, were calcium-induced calcium release sensitive (CICR-sensitive). These findings match recent biochemical studies linking elevated glucosylceramide levels to sensitization of CA2-4 RyaR receptors and 300% potentiation of neuronal CICR sensitivity. In two patients with type 1 GD and parkinsonism, numerous synuclein positive inclusions, similar to brainstem-type Lewy bodies found in Parkinson disease, were also found hippocampal CA2-4 neurons. These findings argue for a common cytotoxic mechanism linking aberrant glucocerebrosidase activity, neuronal cytotoxicity, and cytotoxic Lewy body formation in GD.
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PMID:Neuropathology provides clues to the pathophysiology of Gaucher disease. 1523 32

To study pathological background of dementia in idiopathic Parkinson's disease (PD), 41 autopsy brains (31 cases with and 10 cases without dementia) were investigated. The severity of degenerative changes was evaluated in selected limbic regions (trans- and entorhinal cortex, hippocampus, and amygdala). The densities of Lewy bodies (LBs), Lewy neurites (LNs), neurofibrillary tangles (NFTs), and amyloid neuritic plaques (NPs) were determined on immunohistochemically stained sections using antibodies against alpha-synuclein, tau-protein, and amyloid-beta. Precisely defined modern criteria for selecting study cohort (Newcastle, CERAD and Braak et al.) ensured homogeneity of the study sample and reliability of the results. Comparisons between the cases of Parkinson's disease with dementia (PDD) and those without (PD-only) revealed that the former were characterised by significantly higher densities of LBs and LNs in transentorhinal and entorhinal cortices as well as in the CA2-3 region of the hippocampus and cortical complex of amygdala. In the PDD sub-set we found statistically significant correlation of LBs with LNs counts in CA2-3 region of hippocampus as well as of LBs counts in transentorhinal cortex with LNs counts in CA2-3 hippocampal region. The relationship was also observed between LBs counts in CA2-3 region of the hippocampus and LNs counts in cortical complex of amygdala. Our studies suggest that dementia in PD may be associated with the presence of degenerative changes of PD-type in leading limbic structures, without co-existent Alzheimer's disease (AD). They also imply that LBs and LNs may appear to be morphological hallmarks of the pathological process associated with dementia in PD. LBs and LNs distribution pattern and correlations of LBs with LNs counts in limbic regions observed in our study suggest the cumulative patomechanism of changes dependent on transsynaptic alpha-syn pathology and indicate the spread of the pathological process via axonal transport. The coexistence of the small number of changes of AD-type may exacerbate cognitive deficits in PDD.
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PMID:Limbic neuropathology in idiopathic Parkinson's disease with concomitant dementia. 1553 32


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