Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinicopathologic features of Alzheimer disease, the commonest cause of presenile or senile dementia, are presented. Several of the microscopic brain lesions found in patients with this dementia share the staining properties of amyloid and at least two of these lesions (senile plaque cores and amyloid angiopathy) are biochemically identical. Theories pertinent to the origins of brain amyloid and its role in the pathogenesis of Alzheimer disease are discussed in relation to theories of the cause of this dementia. Possible treatments for Alzheimer disease developed from our knowledge of brain amyloid processing and biochemistry are considered.
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PMID:Brain amyloid and Alzheimer disease. 328 32

The predominant protein of cerebrovascular and plaque core amyloid in Alzheimer's disease, Down's syndrome, hereditary hemorrhage with amyloidosis--Dutch type, sporadic cerebral amyloid angiopathy, and age-related amyloidosis is a unique polypeptide, called beta protein. The length of the plaque amyloid protein was reported to be 42-43 residues, but the complete length of the cerebral vascular amyloid is not known. To clarify this issue, amyloid fibrils from the leptomeninges of an Alzheimer's disease patient were isolated and the primary structure determined. The complete sequence of cerebrovascular beta-amyloid protein, although homologous to the plaque core amyloid protein previously reported, has 39 residues instead of 42. Amino terminal heterogeneity is present but minimal, and it is three residues shorter at the carboxy terminus. These differences are similar to those found in two cases of hereditary hemorrhage with amyloidosis--Dutch type. The differences between vascular and plaque beta-amyloid may reflect diverse processing of the beta protein precursor in the vessel wall and brain parenchyma due to tissue-specific endopeptidases.
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PMID:Differences between vascular and plaque core amyloid in Alzheimer's disease. 329 6

The brain was examined neuropathologically in 16 elderly patients with severe dementia (8 cases of senile dementia, 5 of vascular dementia and 3 of combined senile-vascular dementia), focussing an attention on amyloid angiopathy and and other senile changes. The findings were compared with the results obtained in 10 cases of Alzheimer disease described previously. Amyloid angiopathy was noted in all cases of senile dementia and its distribution was similar to that of Alzheimer disease. The frequency of cerebral amyloid angiopathy in elderly patients with severe dementia was more closely related to disease than to age. One patient each with senile dementia and combined senile-vascular dementia showed markedly advanced amyloid angiopathy. The cases who showed other senile changes (e. g., senile plaque, Alzheimer neurofibrillary tangle, nerve cell deciduation) were frequently seen in patients with Alzheimer disease than in those with senile dementia. Further, there was a tendency that the brain weight was lighter in patients with Alzheimer disease than in those with senile dementia.
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PMID:[Cerebral amyloid angiopathy in senile dementia--a comparison between senile dementia and Alzheimer disease]. 381 39

A case of juvenile Alzheimer's disease is reported with onset at 34 years of age, a clinical course of 6 years, had myoclonic jerks, generalized convulsions, dysarthria and ataxic symptoms. The neuropathological examination indicated kuru-plaques, amyloid angiopathy and grumose alteration (degeneration) in the dentate nucleus. In this case, the plaques in Alzheimer disease is quite rare. This case also demonstrates the complex interrelationship between Alzheimer's disease and various multisystemic degeneration mainly involving the dentate nucleus.
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PMID:Juvenile Alzheimer's disease with myoclonus: amyloid plaques and grumose alteration in the cerebellum. 649 95

The incidence and morphological characteristics of senile plaque and amyloid angiopathy in the cerebrum of six aged cynomolgus monkeys (Macaca fascicularis), 20 to 29 years old, were studied histopathologically and immunohistochemically. By periodic acid methenamine silver stain (PAM) and alkaline Congo red stain, senile plaques were detected in 5 out of 6 cases, and 3 of them were positive for amyloid in the wall of capillaries and arterioles in the cerebral cortex. Senile plaques were classified into three types. Mature plaques, including classical and primitive types, were more frequently observed than the immature diffuse type. Senile plaques were often seen in the cortex of temporal lobe, putamen and head of caudate nucleus. Since mature types of senile plaques were seen frequently around vascular amyloid deposition and no amyloid angiopathy was detected in the areas without senile plaques, the close relation between senile plaque of the mature type and amyloid angiopathy might be considered. All senile plaques and amyloid angiopathy were positively stained immunohistochemically with antibody against amyloid beta-protein (A beta P) 1-40 synthetic peptide, but all diffuse and some primitive plaques were negative for antibody against A beta P 8-17 synthetic peptide. Neither senile plaque nor amyloid angiopathy was detected in the cerebrum of 15 young monkeys, 9 to 11 years old, examined as controls.
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PMID:[Histopathological studies on senile plaques and cerebral amyloid angiopathy in aged cynomolgus monkeys]. 749 37

Recent molecular biological, biochemical and immunohistochemical studies have revealed various novel facts about beta-amyloidosis including its role in the pathogenesis of Alzheimer's disease (AD). Such discoveries include the finding that beta/A4-amyloid protein (beta-AP) is the major component of the amyloid found in senile plaques (SPs) and amyloid angiopathy, the elucidation of the molecular structures of beta-AP and beta-amyloid protein precursor (APP), the finding that point mutations of APP are involved in some cases of familial AD (FAD), the location of genes for FAD, APP and Down's syndrome on chromosome 21, and of other genes relating to AD on chromosomes 19, 14 and 6, and the successful development of Alzheimer-type neuropathology in transgenic mice overexpressing V717F APP, a mutation of APP. Furthermore, the involvement of various proteases and their inhibitors in metabolism of beta-AP have been suggested by: the presence of Kunitz class serine protease and metalloprotease inhibitor domains on some APP, the presence of various proteases and inhibitors in SPs and neurofibrillary tangles (NFTs), the involvement of various proteases in the secretory and endosome/lysosome pathways of APP processing, mutation of the APP gene in hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D), mutation of the cysteine proteinase inhibitor cystatin C gene in HCHWA-I (Iceland type), and abnormal increases of some proteases or the inhibitors in dystrophic neurites of SP, amyloid of SP, and NFTs. Judging from these reports, dysfunction or deregulation of proteolytic systems may play an important role in beta-amyloid formation. Recent studies of beta-amyloid and various proteases and inhibitors in disorders associated with beta-amyloid formation are reviewed including our 'overload hypothesis' as an underlying event in the dysfunction of proteolytic systems. This information should be helpful to identify targets in the development of drugs for the treatment of AD or other age-related disorders.
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PMID:The role of beta-amyloid in the development of Alzheimer's disease. 757 88

Alzheimer's disease (AD) is characterized by a progressive cognitive decline in which memory, initiation, learning and conceptualization are severely affected. The main histopathological alterations are the presence of amyloid beta/A4-containing plaques, tangles and amyloid angiopathy. It is believed that these brain alterations are associated with abnormal expression and/or processing of amyloid precursor protein (APP) and with abnormal assembly of cytoskeletal proteins. Recent quantitative studies with the electron microscope and with immunochemical/immunocytochemical assays, using molecular markers for synaptic proteins, have shown that synaptic loss in the cortex is the major correlate of the patterns of cognitive decline in AD. The synaptic loss in AD is accompanied by neuronal loss and aberrant sprouting, and studies in incipient AD cases have shown that this alteration occurs very early in the progression of the disease preceding tangle formation and neuronal loss. These results suggest that damage to the synaptic terminal plays a central role in the pathogenesis of AD. The mechanisms of synaptic pathology in AD are not yet clear, however, studies in transgenic animal models support the possibility that APP participates in synaptic stabilization and that abnormal metabolism of this molecule could lead to synaptic dysfunction which, in turn, results in neurodegeneration and dementia.
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PMID:Mechanisms of synaptic dysfunction in Alzheimer's disease. 759 45

Recent studies have suggested that advanced glycation end-products (AGE) of the Maillard reaction are associated with amyloidosis in Alzheimer's disease. To evaluate this possibility, the present immunohistochemical study was undertaken to locate AGE in cerebral cortices of Alzheimer's disease, using a monoclonal antibody specific for AGE-proteins. Deposits of beta-amyloid protein within cores of classic senile plaques and vascular walls in amyloid angiopathy showed no AGE-positive reaction, while primitive plaques, coronas of classic plaques and some glial cells were positive for AGE. These findings are inconsistent with the suggestion that AGE may be involved primarily in amyloidosis in Alzheimer's disease.
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PMID:Are advanced glycation end-products associated with amyloidosis in Alzheimer's disease? 852 21

To investigate the process of amyloid beta-protein (A beta) accumulation in cerebral amyloid angiopathy (CAA), the levels of A beta were determined in the soluble fraction of extra- and intracranial blood vessels and leptomeninges obtained at autopsy. Two enzyme immunoassays were employed that are known to sensitively and specifically quantify two A beta species, A beta 1-40 and 1-42(43). A beta was detectable in the intracranial blood vessels and leptomeninges with the latter containing the highest levels, while it was undetectable in the extracranial blood vessels. Thus the levels of soluble A beta correlated well with the predilection sites for CAA. Among individuals aged 20 to 90, the A beta levels in the leptomeninges increased sharply in those aged 50 to 70 and thereafter tended to decline. However, only slight degrees of CAA were detected by immunocytochemistry, even when those leptomeninges contained high levels of A beta comparable with those in Alzheimer's disease. The level of A beta 1-42 was almost always severalfold that of A beta 1-40 in the soluble fraction of leptomeninges. This is in good agreement with the immunocytochemical result showing the presence of A beta 40-negative, A beta 42(43)-positive meningeal vessels. These results indicate that A beta 1-42 is the initially deposited species in CAA and that the disruption of A beta homeostasis precedes A beta deposition in the meningeal vessels.
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PMID:Amyloid beta-proteins 1-40 and 1-42(43) in the soluble fraction of extra- and intracranial blood vessels. 766 28

Brain amyloidosis with abundant beta/A4 protein deposition in plaques and cortical and meningeal vessels is found in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). In contrast to AD, no neuritic pathology or classical congophilic plaques are found in HCHWA-D. Unlike most AD cases, the congophilic angiopathy in HCHWA-D is very severe. It is still unknown whether beta/A4 deposits in plaques and vessels have the same origin. In this study, we have used frozen cortical tissue of HCHWA-D and AD patients to investigate the beta/A4 amyloid protein and the amyloid precursor protein (APP) in different types of plaques and congophilic angiopathy. Immunohistochemical staining was conducted using antibodies against synthetic beta/A4 proteins and antibodies against APP including MAbP2-1, a monoclonal antibody against purified protease nexin-2, which is the secreted form of APP. In contrast to immunohistochemical studies on formalin-fixed, paraffin-embedded tissue, frozen tissue of HCHWA-D patients revealed a very high number of beta/A4 plaques resembling AD. All plaques were of the diffuse type. Double-staining with MabP2-1 and beta/A4 antisera revealed: 1) the presence of APP immunoreactivity in classical plaques and transitional forms; 2) the absence of APP immunoreactivity in diffuse plaques in HCHWA-D and AD; and 3) pronounced APP immunoreactivity in congophilic vessels in HCHWA-D in contrast to weak APP staining in congophilic vessels in AD. Together these findings suggest that: a) the presence of APP in plaques is related to neuritic changes; b) different processes occur in amyloid formation in plaques and vessels; and c) differences exist between the process of amyloid formation in HCHWA-D and AD.
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PMID:Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease. 768 95


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