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

Braak's argyrophilic grains (BAG) are spindle-shaped structures originally described in patients with dementia. We have determined that the prevalence of BAGs in an unselected series of 300 consecutive autopsies of subjects over the age of 30 is 5.6%, or 11.7% if only subjects older than 65 are considered. All the 17 subjects identified were older than 68; 6 received other neuropathological diagnoses of degenerative disease and 11 did not. Only 2 of the latter had shown clinical evidence of mental impairment. Braak's argyrophilic grains were associated with ballooned neurons, superficial linear spongiosis, and gliosis of entorhinal cortex and amygdala. Subcortical neurofibrillary tangles were consistently found in patients with dementia, but not in other subjects. In a separate series studying the prevalence of BAG in neurodegenerative diseases, we found a strong, but not universal association with progressive supranuclear palsy, and to a lesser degree with the lobar atrophies (Pick's disease and corticobasal ganglionic degeneration). Numerous BAG were present in occasional cases of diffuse Lewy body disease, multiple systems atrophy, and motor neuron disease. We conclude that rather than defining a single disease, BAG constitute lesions that accompany several degenerative diseases, but also occur in normal elderly subjects, and rarely in demented subjects without other major histological findings.
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PMID:Prevalence and disease associations of argyrophilic grains of Braak. 903 69

Hallucinations are a common feature of certain degenerative diseases with a risk of dementia such as Alzheimer's disease, Lewy body dementia, and Parkinson's disease. Obtaining valid epidemiological data is nevertheless quite difficult because of methodological problems. As a rule, hallucinations are more prevalent in Lewy body disease than Parkinson's disease or Alzheimer's disease. The prevalence in parkinsonian dementia is about the same as in Lewy body disease. Complex visual hallucinations predominate, auditory or tactile hallucinations are more exceptional. Minor forms (illusions, sensation of presence) are also observed. Recurrence is common, mainly in the evening or at night. Patients with advanced mental impairment generally take the hallucinations for reality. The hallucinations can be associated with psychological and behavioral disorders such as delusionnal idea or identification disorders. It is important to search for other causes of hallucinations such as drugs, ocular disorders, or depression, but many of these disorders are common comorbidities in elderly patients with degenerative disease. There is no unique model fitting all the hypothesized pathogenic mechanisms. Complex visual hallucinations most likely arise from abnormal activation of the extra-striat temporal associative regions, but only hypothetical mechanisms have been proposed. Genetic studies and functional imaging have not provided convincing evidence. Current focus is placed on an imbalance between deficient cholinergic transmission and preserved or augmented monoaminergic transmission at the cortical level, but other neurotransmission systems could be involved. The dream dysregulation mechanism proposed in Parkinson's disease cannot be generalized. The link between cognitive disorders and hallucination is also poorly understood: hallucinations are associated with more severe cognitive impairments or more rapid cognitive deline in Parkinson's disease and Alzheimer's disease, but the association with specific cognitive disorders remains to be fully explored.
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PMID:[Hallucinations and dementia. Prevalence, clinical presentation and pathophysiology]. 1511 51

Diffuse Lewy body disease (DLBD) is a degenerative disease of the nervous system, involving the brain stem, diencephalic nuclei and cerebral cortex, associated with abnormal a-synuclein aggregation and widespread formation of Lewy bodies and Lewy neurites. DLBD presents as pure forms (DLBDp) or in association with Alzheimer disease (AD) in the common forms (DLBDc). Several neurotransmitter abnormalities have been reported including those of the nigrostriatal and mesocorticolimbic dopaminergic system, and central noradrenergic, serotoninergic and cholinergic pathways. The present work examines metabotropic glutamate receptor (mGluR) expression and signaling in the frontal cortex of DLBDp and DLBDc cases in comparison with age-matched controls. Abnormal L-[3H]glutamate specific binding to group I and II mGluRs, and abnormal mGluR1 levels have been found in DLBD. This is associated with reduced expression levels of phospholipase C beta1 (PLCbeta1), the effector of group I mGluRs following protein G activation upon glutamate binding. Additional modification in the solubility of PLCbeta1 and reduced PLCbeta1 activity in pure and common DLBD further demonstrates for the first time abnormal mGluR signaling in the cerebral cortex in DLBD. In order to look for a possible link between abnormal mGluR signaling and a-synuclein accumulation in DLBD, immunoprecipitation studies have shown alpha-synuclein/PLCbeta1 binding in controls and decreased alpha-synuclein/PLCbeta1 binding in DLBD. This is accompanied by a shift in the distribution of a-synuclein, but not of PLCbeta1, in DLBD when compared with controls. Together, these results support the concept that abnormal a-synuclein in DLBD produces functional effects on cortical glutamatergic synapses, which are associated with reduced alpha-synuclein/PLCbeta1 interactions, and, therefore, that mGluRs are putative pharmacological targets in DLBD. Finally, these results emphasize the emergence of a functional neuropathology that has to be explored for a better understanding of the effects of abnormal protein interactions in degenerative diseases of the nervous system.
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PMID:Abnormal metabotropic glutamate receptor expression and signaling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions. 1560 86