Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Hereditary cystatin C amyloid angiopathy (HCCAA), an autosomal dominant form of cerebral amyloid angiopathy (CAA) occurring primarily in Iceland, is characterized by a variant cystatin C amyloid deposition in the walls of cerebral parenchymal and leptomeningeal vessels. Cystatin C is also found to colocalize with amyloid beta/A4 protein in cerebral vessel walls of patients with Alzheimer's disease (AD), sporadic CAA, and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). The abundance of cystatin C deposition in cerebral blood vessel walls suggests that cellular elements of the vessel wall itself may play a role in its deposition. Microvascular changes in the brains of HCCAA patients were investigated by single- and double-label immunohistochemistry. We found that cystatin C amyloid immunoreactivity was present not only in cerebral cortical and leptomeningeal vessels, but also in white matter parenchymal vessels. Cystatin C deposition was more prominent in the media of parenchymal vessels and in the adventitia of leptomeningeal vessels. Smooth muscle (sm) cells were few or could not be identified within vessel walls showing extensive cystatin C deposition, suggesting progressive loss of these cells as cystatin C accumulates. However, in less severely affected vessels, cystatin C was present in cells that also had the phenotype of sm, suggesting that sm cells synthesize or process cystatin C. Cystatin C immunoreactivity was in addition, detected in some neuronal cell bodies throughout the cortex in patients with HCCAA and AD-related CAA. Our results indicate that cellular components of the vessel walls may play an important role in cystatin C deposition, as they do in beta/A4 deposition in AD-related CAA. Cystatin C deposition within the vascular media and adventitia, with associated vessel wall injury as manifested by sm cell loss, represents microvascular degeneration that leads to cerebral hemorrhage.
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PMID:Microvascular degeneration in hereditary cystatin C amyloid angiopathy of the brain. 906

We have developed a new procedure, including three affinity chromatography steps, micro-reversed phase high pressure liquid chromatography (mR-HPLC) and Western blotting/mass spectrometric analysis to study central nervous system (CNS) specific proteins in human cerebro spinal fluid (CSF) in order to find biochemical markers for neuronal and synaptic function and pathology in degenerative brain disorders. After the three affinity chromatography steps, intended to remove interfering serum proteins from CSF, mR-HPLC revealed four major peaks, which by both Western blotting and mass spectrometric analyses were found to correspond to beta 2-microglobulin, cystatin C, transthyretin (TTR) and asialotransferrin. When comparing these peaks in CSF from Alzheimer's disease (AD) patients and age-matched healthy controls, a reduction of the brain-specific TTR was found. Therefore we quantified TTR in CSF and serum samples from 8 patients with early onset AD (EAD), 18 patients with late onset AD (LAD), 8 patients with vascular dementia (VAD) and 18 healthy individuals using a nephelometric method. CSF-TTR was divided into barrier-dependent and barrier-independent TTR. The barrier-independent i.e. brain-specific TTR was significantly reduced in the EAD group compared to the controls. Transthyretin has been found to be present in the senile plaques in AD, and to specifically bind to beta/A4 protein, the major component of the amyloid deposits in AD. Therefore, the reduction of the transthyretin-isoform in CSF in AD may reflect an absorption of transthyretin to the amyloid deposits in the senile plaques.
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PMID:A new procedure for detecting brain-specific proteins in cerebrospinal fluid. 944 70

Various secondary microvascular degenerative and inflammatory alterations may complicate cerebral amyloid angiopathy (CAA) and contribute to the morbidity of CAA-associated stroke. We have investigated the severity of CAA-associated microangiopathy in a genetically determined Dutch form of CAA (HCHWA-D) that has major similarities to the type of CAA that more commonly occurs with aging or Alzheimer's disease (AD). The presence and extent of the following vascular abnormalities was assessed: (1) hyalinization/fibrosis, (2) microaneurysm formation, (3) chronic (especially lymphocytic) inflammation, (4) perivascular multinucleated giant cells/granulomatous angiitis, (5) macrophages/histiocytes within the vessel wall, (6) vessel wall calcification, (7) fibrinoid necrosis, and (8) mural or occlusive thrombi. (Of these, calcification of CAA-affected vessel walls has, to our knowledge, been described in only a single patient with CAA-associated cerebral hemorrhage.) Some of the changes, such as histiocytes in blood vessel walls and the relationship of vascular hyalinosis to amyloid beta/A4 protein deposition, were highlighted by immunohistochemistry. By assessing the numbers of sections in which the changes were present for each case, a 'score' reflective of CAA-associated angiopathy could be obtained. This 'score' was reproducible among several observers. We suggest that it might also be applicable to quantifying severe CAA and related microvascular degenerative changes in patients with AD. beta/A4 immunoreactivity was often sparse and adventitial (or almost absent) in severely hyalinized arterioles and microaneurysms. However, macrophages were prominent in the walls of such vessels and may play a role in the pathogenesis and progression of CAA-related microvasculopathy.
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PMID:Secondary microvascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). 954 88