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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)

The extracellular matrix protein heparin sulfate proteoglycans (HSPG) has been found in the neurofibrillary pathology of Alzheimer disease. This study was performed to determine if similar proteoglycans might be present in the fibrillary inclusions of other neurodegenerative diseases. Basic fibroblast growth factor (bFGF) binding to heparinase sensitive sites was used as an assay for HSPGs. We found that the inclusions of Pick and Parkinson diseases as well as progressive supranuclear palsy contained heparinase sensitive bFGF binding sites while the inclusions of diffuse Lewy body disease lacked bFGF binding sites. These findings indicate that HSPG's interactions and possible role in the formation of intraneuronal inclusions are not limited to Alzheimer disease.
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PMID:Basic fibroblast growth factor binds to filamentous inclusions of neurodegenerative diseases. 162 22

The discovery of a specific association between nerve growth factor (NGF) and basal forebrain cholinergic neurons (BFCNs) marks the beginning of a new era of research into neurodegenerative diseases such as Alzheimer disease (AD). Degeneration of BFCNs appears to be one of the earliest and most prominent neuropathological features of a broad range of diseases of the human brain that give rise to loss of memory and dementia (including, in addition to Alzheimer disease, Parkinson disease, Lewy body dementia, progressive supranuclear palsy, dementia pugilistica, olivopontocerebellar atrophy, and Wernicke-Korsakoff syndrome). Selective localization of NGF receptors on BFCN, the relatively high levels of NGF mRNA in BFCN target areas, and numerous effects of exogenous NGF in vivo and in vitro provide overwhelming evidence that the structure and function of BFCNs in the adult brain are dependent on this molecule. The question then arises as to how this special relationship is disturbed in the diseased human brain? Initial investigations in AD have already indicated a normality of NGF mRNA and retention of receptors in the basal forebrain region. Interpretation of these results and the therapeutic relevance of NGF obviously depend upon future developments in understanding the role of NGF in the normal and pathological brain.
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PMID:Nerve growth factor and the basal forebrain cholinergic system: a link in the etiopathology of neurodegenerative dementias? 218 Apr 39

A review for the non-specialist. The proportion of dementia of different types varies in different investigations, illustrating the difficulty of classification. Recently genetic variants of amyloid precursor protein and apolipoprotein E have been found in some of the families with familial Alzheimer's disease. Cortical Lewy body disease and frontotemporal dementia have been described recently, indicating that Alzheimer's disease comprises more diseases. When diagnosing dementia, it is important to identify confusions, depressions, the vascular dementias and the potentially reversible ones. The treatment may include reducing drug therapy, prophylactic treatment of thromboembolic or hypertensive disease, care, information to the family and carers, and sometimes drug treatment for psychiatric symptoms. In the near future effective treatment of some of the primary degenerative dementias may become possible. It will then be necessary to make a more specified diagnosis at an early stage.
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PMID:[Dementia--where are we today?]. 775 92

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cortical neuritic pathology of Huntington's disease. 777 Jan 16

The Lewy body variant of Alzheimer disease (LBV) is a distinct category of dementia which, unlike pure diffuse Lewy body disease (DLBD), meets clinical and neuropathologic criteria for Alzheimer disease (AD) but differs from pure AD in having a neocortical predominance of diffuse and neuritic plaques (NP), with very few neurofibrillary tangles (NFT). We investigated the immunoreactivity of NP with a monoclonal antibody against paired helical filaments (PHF) composed of phosphorylated microtubule associated protein tau. With routine thioflavin-S preparations, 12 LBV and 14 AD cases had similar numbers of NP, but the LBV had significantly (P < 0.05) fewer NFT per microscopic field in the midfrontal cortex. Among subjects with midfrontal NFT, 81-84% of NP in AD and LBV were anti-PHF positive. Among subjects without midfrontal NFT, 52% of NP in AD but only 12% of NP in LBV cases were anti-PHF positive (P < 0.05). LBV differs from AD in that its NP generally do not contain PHF, unless they are accompanied by neocortical NFT.
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PMID:Neuritic plaques in the Lewy body variant of Alzheimer disease lack paired helical filaments. 908 76

In the authors experience of a memory clinic, about 2/3 of the patients fulfilled the criteria for dementia and among the demented patients 2/3 had probable Alzheimer's disease. Vascular dementia is the second cause of dementia in elderly people, but two other degenerative disorders fulfilling the NINCDS-ADRDA criteria for Alzheimer disease (Mc Khann et al., 1984) account for degenerative dementia. There is now a consensus for the clinical diagnosis and the neuropathological aspects of these two diseases: Dementia with Lewy Bodies (Mc Keith et al., 1996) and fronto-temporal dementia (the Lund and Manchester groups, 1994). The authors emphasize the clinical aspects of those two diseases at an early stage in comparison with dementia of Alzheimer type.
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PMID:[Role of Alzheimer's type dementia among dementias of the elderly]. 910 53

The prevalence of dementia in the elderly (65 years old and over) was estimated at 6.3% (men 5.8%, women 6.7%) in Japan in 1985. Epidemiological studies done in several prefectures in 1989 and later showed a tendency for patients with Alzheimer's disease (AD) to outnumber those with vascular dementia (VD); the VD/AD ratio was less than 1.0 in over half of the surveys. A pathologic study (Kosaka 1996) of 79 patients with dementia revealed that AD was more common than VD, although clinical diagnoses were the reverse, which indicated that VD is still overdiagnosed in Japan. Diffuse Lewy body disease was observed in 15% of those patients without correct clinical diagnosis. Many biological markers for AD have been reported. We used 1H-magnetic resonance spectroscopy of the brain and found that the ratio of N-acetyl aspartate to creatine in AD patients was significantly smaller than that in age-matched controls without dementia. Based on genetic studies, AD is classified into five types. These are related to chromosomes 14 (presenilin-1), 21 (beta APP gene), 1 (presenilin-2), 19 (epsilon 4 alleles), and other. The causes of most sporadic cases remain unclear. Tacrine is the only drug authorized in the U.S.A. for treatment of AD, but it is not used in Japan because of its side effects. Many other drugs to treat dementia are now in nationwide clinical trials although only four are in phase III. Therefore, rehabilitation therapy is mandatory and details of that therapy should be individualized. A new system of public insurance for nursing care may be implemented by the government.
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PMID:[Dementia--causes, diagnosis, treatment, and care]. 912 81

Complement-activated oligodendroglia (CAOs) are thought to represent complement bearing damaged oligodendroglia for opsonization. The interrelationship between CAOs and amyloid deposits was examined by immunohistochemistry in the parietal lobe of patients with Parkinson's disease, diffuse Lewy body disease, and pallido-nigro-luysial atrophy. In all brains, the anti-C4d antibody stained numerous CAOs. Anti-beta-amyloid protein (anti-A beta) antibody revealed moderate numbers of senile plaques, including some of the classical type. In both the grey and the white matter amyloid deposits were frequently associated with the myelinated axons of CAOs. CAOs were occasionally associated with phagocytosing microglial cells. Immunoelectron microscopy also showed a close relationship between phagocytosing microglia and A beta deposition. On some occasions. A beta deposits were seen in C4d-positive oligodendroglial cell bodies. These results indicate that damaged myelinated axons, which contain accumulated amyloid precursor protein, are the source of A beta, and that CAOs may be initial targets for A beta deposits forming the classical senile plaques.
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PMID:Interrelationship between beta-amyloid deposition and complement-activated oligodendroglia. 929 27

The lesions of Alzheimer disease (AD) consist of synapse and neuron loss associated with progressive deposition of amyloid as diffuse and neuritic plaques and accumulating tau abnormalities in the form of neurofibrillary tangles and neuropil threads. Diagnostic criteria for Alzheimer disease constitute arbitrary cut-off levels above which AD is deemed to exist, and below which lesser amounts of the same abnormalities are relegated to the nebulous category of aging changes. Demanding neocortical tangles for a diagnosis of AD sacrifices sensitivity on the altar of specificity, since, while such lesions usually represent an advanced stage in the orderly evolution of AD, lighter burdens of plaque-predominant AD pathology with tangles confined to the medial temporal lobe can cause dementia when associated with concomitant synapse loss. Such muted AD pathology typifies the Lewy body variant of AD, and it serves to segregate it from pure Lewy body disease. We endorse the semiquantitative neuritic-plaque based criteria from CERAD for routine diagnosis, and Braak staging with descriptive profiling of AD lesions in a research context.
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PMID:Position paper on diagnostic criteria for Alzheimer disease. 933 Sep 89

The Lewy body variant of Alzheimer disease (LBV) occupies a messy middle ground between Alzheimer disease (AD) on the one hand, and pure Lewy body diseases (Parkinson's disease or diffuse Lewy body disease), on the other. In addition to brainstem and neocortical Lewy bodies, LBV brains have enough neocortical neuritic plaques to meet diagnostic criteria for AD. However, neurofibrillary pathology in LBV is modest, since tangle densities in LBV are typically intermediate between AD and age-matched controls or pure Lewy body disease brains. Apolipoprotein E-4 is overrepresented in LBV, as it is in AD but is not in PD or diffuse Lewy body disease (DLBD). Neurologically, LBV patients often display sufficient parkinsonian signs to separate them from AD, but these findings are usually too subtle to warrant clinical diagnoses of Parkinson's disease (PD). Neuropsychological deficits in LBV include a subcortical dementia pattern similar to DLBD, and more severe global cognitive impairment reminiscent of AD.
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PMID:The Lewy body variant of Alzheimer disease. 947 Jan 30


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