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)

Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.
 ...
PMID:Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD. 165 14

The frequency of the apolipoprotein E (ApoE) epsilon 4 allele and its relationship with coexistent Parkinson's disease (PD) neuropathology in Alzheimer's disease (AD) have not been extensively explored. We determined ApoE genotype in 100 dementia patients with neuropathologically confirmed AD with and without concomitant Parkinson's disease (PD) changes (nigral degeneration and Lewy bodies at various sites). Fifty "AD+PD" patients were matched closely with 50 "pure AD" patients for age, sex, and duration of dementia. We found identical overrepresentation of the epsilon 4 allele in the two groups: 72% of the patients in each group had at least one ApoE epsilon 4 allele, compared with approximately 25% in the general population (p < 0.005) and in our institutional autopsy population (p < 0.001). Age at onset varied inversely with epsilon 4 allele dosage in men but not in women in both the AD and the AD+PD groups. As with amyloid deposition and plaque frequency in AD, we observed an association between epsilon 4 dosage and PD-related changes. Specifically, the severity of ubiquitin-positive neuritic change in CA2/3 of the hippocampus, but not the frequency of cortical Lewy bodies, varied significantly with epsilon 4 dosage in the AD+PD cases.
 ...
PMID:Alzheimer's disease with and without coexisting Parkinson's disease changes: apolipoprotein E genotype and neuropathologic correlates. 750 Nov 46

We investigated CA2/3 ubiquitin-immunoreactive neurites in 120 cases of diverse neurodegenerative diseases. This neuritic change occurred in 25 of 30 cases of Alzheimer's disease (AD) with coexistent Parkinson's disease (PD) changes, as well as two cases of PD and two cases of progressive supranuclear palsy. All 29 cases with neuritic change showed cortical Lewy bodies. Neuritic change was absent in 86 cases of neurodegenerative diseases without Lewy bodies, including 66 cases of pure AD. Thus, ubiquitin-immunoreactive CA2/3 neurites and cortical Lewy bodies, frequently coexist; this association appears to be independent of the presence or absence of coexistent pathologies, eg, AD. Moreover, in and of itself, nigral degeneration without Lewy bodies, such as that encountered in other (non-PD) movement disorders, apparently is not associated with CA2/3 neuritic change.
 ...
PMID:Ubiquitin-positive CA2/3 neurites in hippocampus coexist with cortical Lewy bodies. 767 45

One of the characteristic histological features of Parkinson's disease (PD), with or without dementia, is the presence of Lewy bodies (LBs) in the brainstem and neocortical and limbic structures. They are often accompanied by Alzheimer type pathology (ATP). In the present retrospective study the clinical features and post-mortem findings of 18 consecutive and unselected PD patients were compared, with special reference to the frequent but not exclusive association of LBs with ATP in Lewy body disease (LBD). LBD is the term applied to a particular pattern of neuronal degeneration associated with LBs. In this study of idiopathic PD patients ATP seems to be the major determinant of the cognitive decline in most patients. Cortical Lewy Bodies (CLBs) were present in all patients reviewed, whether or not dementia was present. It was not possible to distinguish a specific pattern in the cognitive or psychopathological symptoms of dementia that would differentiate LBD from Alzheimer's disease (AD). Although in most cases hippocampal CA2-3 ubiquitin immunoreactive neurites were observed, here again there was no correlation with the presence of dementia.
 ...
PMID:'Lewy body disease': clinico-pathological correlations in 18 consecutive cases of Parkinson's disease with and without dementia. 778 67

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.
 ...
PMID:Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. 791 27

Genetic influences are thought by many to play an important role in the cause of Parkinson's disease. We studied two closely intermarried families (Family G) whose ancestors immigrated to the United States from Russia. We investigated this family clinically, genealogically, and pathologically. Our pedigree contained 102 members spanning six generations, with 10 affected individuals and 1 affected spouse. Detailed telephone interviews were conducted with affected individuals, with their spouses, and with their at-risk siblings. Medical records of deceased and living affected patients were collected. Physical examinations were performed on 7 at-risk and 5 affected persons. Typical levodopa-responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes was seen in 4 members, dementia was present in 3, and 3 had both dementia and parkinsonism. An autopsy completed on 1 individual, our index case, demonstrated Lewy bodies in the brainstem and neocortex and ubiquitin-positive neuritic degeneration in the CA2-3 region of the hippocampus, consistent with the limbic (transitional) form of Lewy body disease. This family is distinct both clinically and pathologically from several previously reported parkinsonian kindreds.
 ...
PMID:Familial parkinsonism, dementia, and Lewy body disease: study of family G. 938 76

Severe dementia affects 10 to 20% of all patients with Parkinson's disease (PD) and is particularly common in those aged 65 years and over. In a clinicopathologic study, we correlated Mini-Mental State Examination scores and DSM-III dementia ratings with the density of Lewy bodies, Lewy neurites, neurofibrillary tangles, neuritic plaques, gliosis, and neurons in the hippocampus and amygdala of 27 PD patients without Alzheimer's disease changes. Cortical Lewy body densities were examined in the anterior cingulate gyrus. The degree of cognitive impairment was correlated with the density of Lewy neurites in the CA2 hippocampal field, raising the possibility that disruption of the connection between the dentate gyrus, entorhinal cortex, septal nuclei, and hypothalamus and the CA1 field contributes to dementia in PD.
 ...
PMID:The relationship between dementia and direct involvement of the hippocampus and amygdala in Parkinson's disease. 981 13

Lewy body disease (LBD) is a progressive neurological disorder with parkinsonism, having many Lewy bodies (LBs) and degenerative changes. LBD is classified into the three types according to the distribution of LBs: "brain-stem type", "transitional type" and "diffuse type". The brain-stem type is identical to classical Parkinson's disease (PD). The diffuse type is nominated as "diffuse Lewy body disease" (DLBD). DLBD is a neuropathological entity, characterized by abundant LBs not only in the basal ganglia and brain-stem but in the cerebral cortex, combined with senile changes. Juvenile onset DLBD is called "pure form" of DLBD because of no or few senile changes. The LBs are present in the amygdala, nucleus basalis of Meynert, hypothalamic nuclei, substantia nigra, nucleus paranigralis, locus caeruleus, dorsal vagal nucleus and reticular nuclei. The cerebral LBs are numerous in the parahippocampal gyrus, cingular gyrus, and insular, frontal and temporal cortices. The LBs show immunoreactivity to ubiquitin and the ubiquitin-immunoreactive neurites in the CA2-3 region appear to be specific for DLBD. The clinical features of DLBD in the senium are progressive dementia, psychotic state, parkinsonism and autonomic signs. In general, progressive dementia is an initial symptom, followed by parkinsonism in the later stage. Some show progressive autonomic failure. A few present respiratory failure or vocal cord palsy resulting in sudden death in DLBD. DLBD is characterized neurochemically by severe affection of multiple neurotransmitters networks. In DLBD an impairment of the innominato-cortical cholinergic and mesocortical dopaminergic system, differentiating from Alzheimer's disease and PD, may play an important role in developing disease process.
 ...
PMID:[Diffuse Lewy body disease]. 957 69

A mutation in the alpha-synuclein gene has recently been linked to some cases of familial Parkinson's disease (PD). We characterized the expression of this presynaptic protein in the midbrain, striatum, and temporal cortex of control, PD, and dementia with Lewy bodies (DLB) brain. Control brain showed punctate pericellular immunostaining. PD brain demonstrated alpha-synuclein immunoreactivity in nigral Lewy bodies, pale bodies and abnormal neurites. Rare neuronal soma in PD brain were immunoreactive for alpha-synuclein. DLB cases demonstrated these findings as well as alpha-synuclein immunoreactivity in cortical Lewy bodies and CA2-3 neurites. These results suggest that, even in sporadic cases, there is an early and direct role for alpha-synuclein in the pathogenesis of PD and the neuropathologically related disorder DLB.
 ...
PMID:Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson's disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. 960 Feb 26

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In AD, susceptible neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific lesional pattern of both illnesses accrues slowly over time and remains remarkably consistent across cases. In AD, six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. The pathologic process commences in the transentorhinal region (clinically silent stages I and II), then proceeds into adjoining cortical and subcortical components of the limbic system (stages III and IV - incipient AD), and eventually extends into association areas of the neocortex (stages V and VI - fully developed AD). During the course of PD, important components of the limbic system undergo specific lesions as well. The predilection sites include the entorhinal region, the CA2-sector of the hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate areas, agranular insular cortex (layer VI), and - within the amygdala - the accessory cortical nucleus, the ventromedial divisions both of the basal and accessory basal nuclei, and the central nucleus. The amygdala not only generates important projections to the prefrontal association areas but also exerts influence upon all non-thalamic nuclei which in a non-specific manner project upon the cerebral cortex and upon the nuclei regulating endocrine and autonomic functions. All these amygdala-dependent structures themselves exhibit severe PD-specific lesions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Similarly, AD-related pathology up to stage III may be asymptomatic as well. Fully developed PD with concurring incipient AD, however, is likely to cause impaired cognition. Presently available data support the view that the occurrence of additional lesions in the form of AD stage III (or more) destruction is the most common cause of intellectual decline in PD.
 ...
PMID:Pattern of brain destruction in Parkinson's and Alzheimer's diseases. 961 89


1 2 3 4 Next >>