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)

Senile dementia of Lewy body type or Lewy body dementia (SDLT or LBD) is defined as a Lewy body associated disease presenting in the elderly primarily with dementia with variable extrapyramidal disorder. Characteristic clinical symptoms include fluctuating cognitive impairment, psychotic features such as hallucinations and a particular sensitivity to neuroleptic medication. Although apolipoprotein e4 allele is increased 2-3 fold in SDLT (as in Alzheimer's disease) and beta-amyloidosis occurs in most cases, the most robust neurobiological correlate of the dementia so far identified appears to be extensive cholinergic deficits in the neocortex. This is consistent with previously reported correlations between cortical cholinergic activity and dementia in Parkinson's disease (PD) and Alzheimer's disease. There is also a significant interaction between the density of limbic cortical Lewy bodies and dementia in both SDLT and PD, although the cortical neuronal population affected remains to be identified. Cortical Lewy body density is positively correlated with the age of disease onset in PD and SDLT. This may account for the increased incidence of psychiatric syndromes, as opposed to extrapyramidal disorder in Lewy body disease with advancing age as may age-related loss of cholinergic activity in cortical areas such as the hippocampus.
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PMID:Lewy body dementia--clinical, pathological and neurochemical interconnections. 947 Jan 31

Measurement of local cerebral glucose metabolism (lCMRGlc) by positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard technique during the past 20 years and is now available at many university hospitals in all highly developed countries. Many studies have documented a close relation between lCMRGlc and localized cognitive functions, such as language and visuoconstructive abilities. Alzheimer's disease (AD) is characterized by regional impairment of cerebral glucose metabolism in neocortical association areas (posterior cingulate, temporoparietal and frontal multimodal association cortex), whereas primary visual and sensorimotor cortex, basal ganglia, and cerebellum are relatively well preserved. In a multicenter study comprising 10 PET centers (Network for Efficiency and Standardisation of Dementia Diagnosis, NEST-DD) that employed an automated voxel-based analysis of FDG PET images, the distinction between controls and AD patients was 93% sensitive and 93% specific, and even in very mild dementia (at MMSE 24 or higher) sensitivity was still 84% at 93% specificity. Significantly abnormal metabolism in mild cognitive deficit (MCI) indicates a high risk to develop dementia within the next two years. Reduced neocortical glucose metabolism can probably be detected with FDG PET in AD on average one year before onset of subjective cognitive impairment. In addition to glucose metabolism, specific tracers for dopamine synthesis (18F-F-DOPA) and for (11C-MP4A) are of interest for differentiation among dementia subtypes. Cortical acetylcholine esterase activity (AChE) activity is significantly lower in patients with AD or with dementia with Lewy bodies (DLB) than in age-matched normal controls. In LBD there is also impairment of dopamine synthesis, similar to Parkinson disease.
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PMID:PET studies in dementia. 1279 Mar 55

Olfactory dysfunction increases with disease severity in Alzheimer's disease (AD), is early and independent of disease severity in Parkinson's disease (PD), but is absent in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Previous histopathologic studies of olfactory bulbs in AD have shown neurofibrillary tangles (NFTs) and senile plaques while Lewy bodies (LBs) have been described in PD. Little is known about olfactory bulb pathology in PSP and CBD. Tau and alpha-synuclein pathology was assessed with immunohistochemistry in olfactory bulbs of AD (N=15), Lewy body disease (LBD; N=10), LBD with concurrent AD (AD/LBD; N=19), PSP (N=27), CBD (N=3) and cases with no significant neurodegenerative pathology (NSP; N=15). The Braak NFT stage, counts of senile plaques and NFT in cortical and hippocampal sections, and counts of LBs in amygdala and cortical sections were recorded for each case. Apolipoprotein E (APOE) genotypes were determined on DNA prepared from frozen brain tissue. All AD and AD/LBD cases and nine of 10 LBD cases had tau pathology in the anterior olfactory nucleus (AON), but it was uncommon in PSP (9/27), CBD (0/3) and NSP (5/15). Multiple linear regression analysis demonstrated that tau pathology in the AON correlated with Braak stage (P<0.001), cortical LB counts (P<0.001), as well as APOE epsilon4. Tau pathology is common in the olfactory bulb of AD and LBD but is minimal or absent in PSP and CBD. It correlates with APOE epsilon4, severity of tau pathology in the brain and surprisingly with cortical and amygdala LBs, suggesting a possible synergistic effect between tau and synuclein in the AON in cases with both pathologic processes.
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PMID:Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein epsilon4. 1450 42

Disorders with Lewy body (LB) formation, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein accumulation in the neuronal cell body. Recent studies have suggested that in addition to LBs, alpha-synuclein might accumulate more widely throughout the neurons and their processes, leading to neurodegeneration and functional impairment. The precise patterns of alpha-synuclein accumulation in vivo, however, and its relationship with subcellular neuronal alterations such as lysosomal pathology are not completely clear. To this end, we developed transgenic (tg) in vivo and in vitro models expressing a stable enhanced green fluorescent protein (eGFP) tagged in the C-terminal site of a human (h)alpha-synuclein construct under the regulatory control of the platelet-derived growth factor-beta (PDGFbeta) promoter and carried out confocal, ultrastructural, and biochemical studies. In tg mice, confocal studies demonstrated a wide distribution of halpha-synuclein-eGFP in the neuronal cell bodies, axons, and presynaptic terminals. In several neuronal cell bodies and their neurites, halpha-synuclein-eGFP was found not only as inclusions but also as discrete granular structures that in double-labeling studies colocalized with antibodies against halpha-synuclein and the lysosomal marker cathepsin D. Consistent with these findings, ultrastructural analysis showed that halpha-synuclein-eGFP overexpression resulted in the accumulation of electrodense inclusions and laminated bodies suggestive of lysosomal pathology, and that the halpha-synuclein-eGFP protein was more abundant in the lysosomal fractions of the tg animals. Taken together, these findings support the notion that enhanced visualization of alpha-synuclein utilizing a hybrid eGFP molecule reveals a more widespread accumulation of this molecule in several neuronal compartments, promoting lysosomal dysfunction. Furthermore, the PDGFbeta-halpha-synuclein-eGFP tg model might be a valuable tool in testing new treatments for LBD in a fast and reliable manner.
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PMID:Lysosomal pathology associated with alpha-synuclein accumulation in transgenic models using an eGFP fusion protein. 1576 23

Parkinson's disease (PD) is the most common cause of parkinsonism. Parkinsonism is characterized by resting tremor, bradykinesia, rigidity and gait impairment. There is no specific diagnostic test for PD and it is important for clinicians to understand the clinical signs which help to distinguish PD from parkinsonism. It is equally important to be aware of the clinical signs which can be an indication that the diagnosis is not PD. These so-called Parkinson-plus syndromes include progressive supranuclear palsy (PSP), multiple systems atrophy (MSA), corticobasal degeneration (CBD), vascular parkinsonism (VP) and parkinsonism with dementia (Lewy body dementia, LBD). The differential diagnosis of parkinsonism will be discussed. Initiating pharmacologic therapy for PD must take into consideration the degree of dysfunction the patient is experiencing, the question of neuroprotection, the degree of motor response required, and the potential complications of long-term treatment. Neuropro-tective trials of coenzyme Q10 (CoQ), vitamin C, vitamin E, monoamine oxidase B inhibitors (MAO-I) and dopamine agonists do not support the use of any of these drugs for a neuroprotective effect. There is recent supportive evidence that levodopa may have a neuroprotective effect. Either dopamine agonists or levodopa may be initiated. Dopamine agonists are associated with fewer motor fluctuations and dyskinesias, while levodopa is associated with better motor performance. Initiation of therapy should be tailored to individual patients with the emphasis on symptom control, with the hope that new approaches to treatment of PD (including neuroprotection) will be forthcoming.
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PMID:Parkinson's disease. Diagnosis and the initiation of therapy. 1617 58

Positional asphyxia refers to a situation where there is compromise of respiration because of splinting of the chest and/or diaphragm preventing normal respiratory excursion, or occlusion of the upper airway due to abnormal positioning of the body. Examination of autopsy files at Forensic Science SA revealed instances where positional asphyxia resulted from inadvertent positioning that compromised respiration due to intoxication, multiple sclerosis, epilepsy, Parkinson disease, Steele-Richardson-Olszewski syndrome, Lafora disease and quadriplegia. While the manner of death was accidental in most cases, in one instance suicide could not be ruled out. We would not exclude the possibility of individuals with significant cardiac disease succumbing to positional asphyxia, as cardiac disease may be either unrelated to the terminal episode or, alternatively, may result in collapse predisposing to positional asphyxia. Victims of positional asphyxia do not extricate themselves from dangerous situations due to impairment of cognitive responses and coordination resulting from intoxication, sedation, neurological diseases, loss of consciousness, physical impairment or physical restraints.
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PMID:Conditions and circumstances predisposing to death from positional asphyxia in adults. 1876 6

Any complaints from a patient about their memory should be examined. Diagnosis is based on international criteria. The basic evaluation consists of the medical history, clinical evaluation, cognitive tests and brain imaging, especially using MRI. When a diagnosis of Alzheimer's disease, AD with cerebrovascular disease or with Lewy Body disease, or Dementia associated with Parkinson's disease or LBD is made, evidence based medical therapy is indicated as part of comprehensive care. An acetylcholinesterase inhibitor or memantine can be used. These drugs are ineffective in the case of frontotemporal degenerations. For severe behavioural disorders, other psychoactive medications can be applied.
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PMID:[Update on current care guidelines. The diagnosis and medical treatment of memory disorders]. 2107 63

Recent advances have been made in defining the genetic and molecular basis of dementia with Lewy bodies (DLBs) and related neurodegenerative disorders such as Parkinson's disease (PD) and Parkinson's disease dementia (PDD) which comprise the spectrum of "Lewy body disorders" (LBDs). The genetic alterations and underlying disease mechanisms in the LBD overlap substantially, suggesting common disease mechanisms. As with the other neurodegenerative dementias, early diagnosis in LBD or even identification prior to symptom onset is key to developing effective therapeutic strategies, but this is dependent upon the development of robust, specific, and sensitive biomarkers as diagnostic tools and therapeutic endpoints. Recently identified mutations in the synucleins and other relevant genes in PD and DLB as well as related biomolecular pathways suggest candidate markers from biological fluids and imaging modalities that reflect the underlying disease mechanisms. In this context, several promising biomarkers for the LBD have already been identified and examined, while other intriguing possible candidates have recently emerged. Challenges remain in defining their correlation with pathological processes and their ability to detect DLB and related disorders, and perhaps a combined array of biomarkers may be needed to distinguish various LBDs.
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PMID:Bridging molecular genetics and biomarkers in lewy body and related disorders. 2176 Sep 90

This research is based on the brain bank project, which combines prospective clinical follow ups and retrospective neuropathological studies. Pathology of idiopathic Parkinson disease (PD) can be summarized as a spectrum of Lewy body (LB) disease (LBD) comprising PD, dementia with LB (DLB) and pure autonomic failure (PAF). Recently core protein component of LB is proved to be alpha-synuclein, which is truncated, phosphorylated and ubiquitinated. Immunohistochemistry with anti-phosphorylated alpha-synuclein (psyn) antibody visualizes LB pathology with previously unattained high sensitivity and specificity, and enables pathological studies of peripheral autonomic nervous system as well as central nervous system. Recently Braak et al proposed ascending extension hypothesis of LB pathology, based on consecutive autopsy cases of PD and normal controls without dementia. However, not excluding demented cases, we found olfactory-amygdala extension pathway of LB pathology, which is independent from Braak's ascending pathway. We propose that abnormal seeding and aggregation of alpha-synuclein could be formed in peripheral autonomic nervous system or olfactory bulb and extend via neural network and form clinical phenotype of LBD.
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PMID:[Neuropathology]. 2227 22

Patients exhibiting the classic manifestations of parkinsonism - tremors, rigidity, postural instability, slowed movements and, sometimes, sleep disturbances and depression - may also display severe cognitive disturbances. All of these particular motoric and behavioral symptoms may arise from Parkinson's disease [PD] per se, but they can also characterize Lewy Body dementia [LBD] or concurrent Parkinson's and Alzheimer's diseases [PD & AD]. Abnormalities of both movement and cognition are also observed in numerous other neurologic diseases, for example Huntington's Disease and the frontotemporal dementia. Distinguishing among these diseases in an individual patient is important in "personalizing" his or her mode of treatment, since an agent that is often highly effective in one of the diagnoses (e.g., L-dopa or muscarinic antagonists in PD) might be ineffective or even damaging in one of the others. That such personalization, based on genetic, biochemical, and imaging-based biomarkers, is feasible is suggested by the numerous genetic abnormalities already discovered in patients with parkinsonism, Alzheimer's disease and Huntington's disease (HD) and by the variety of regional and temporal patterns that these diseases can produce, as shown using imaging techniques.
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PMID:Personalized medicine strategies for managing patients with parkinsonism and cognitive deficits. 2299 12


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