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)

Plaque-like lesions and amyloid angiopathy were investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to beta amyloid protein (A beta), beta protein precursor (beta PP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein (GFAP)], enzymehistochemical (acid phosphatase) and silver [methenamine silver (MS) and Palmgren] staining methods. Whereas A beta- and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuritic or congophilic plaques, which were acid phosphatase and cathepsin D positive and contained beta PP-, synaptophysin- and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno- and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.
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PMID:Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology. 783 31

The evolvement of amyloid beta (Abeta) deposition in the frontal cerebral cortex of 24 patients of increasing age with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) was studied using end-specific monoclonal antibodies to Abetax-42 (Abeta42) or Abetax-40 (Abeta40) and markers for degenerating neurites. Abeta42 immunostaining revealed parenchymal Abeta deposits with a heterogeneous morphology and distribution, i.e., clouds, fine/dense diffuse, coarse, and homogeneous plaques. Clouds and diffuse plaques were associated with glial Abeta granules. Abeta40 labeling was absent in clouds/fine diffuse plaques, inconsistent and variably intense in dense diffuse/coarse plaques and consistent in homogeneous plaques. In a subset of Abeta40-positive plaques, degenerating neurites--without tauopathy--and/or amyloid cores were observed. Electron microscopy revealed no apparent amyloid fibrils in fine diffuse plaques, small bundles of fibrils in dense diffuse/homogeneous plaques, and amyloid masses in coarse plaques. The parenchymal Abeta pathology was age-related: the ratio of fine to dense diffuse plaques decreased with age, clouds were limited to younger patients; coarse plaques to the oldest old. Homogeneous/cored plaques were present most consistently in older patients. Plaque density did not increase with age. Vascular Abeta deposits stained for both Abeta species, but exclusively Abeta42-positive, presumably recent deposits were also observed. This study suggests that HCHWA-D is a model of plaque evolution in which clouds leave fine diffuse plaques, which may become dense diffuse and ultimately coarse or homogeneous plaques.
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PMID:Age-related plaque morphology and C-terminal heterogeneity of amyloid beta in Dutch-type hereditary cerebral hemorrhage with amyloidosis. 1078 40

The amyloid beta-protein (Abeta) E22Q mutation of the rare disorder hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) causes severe cerebral amyloid angiopathy (CAA) with hemorrhagic strokes of mid-life onset and dementia. The mutation does not affect total Abeta production but may alter the Abeta1-42:Abeta1-40 ratio, and affect the proteolytic degradation of Abeta and its transport across the blood-brain barrier. Abeta E22Q aggregates faster into more stable amyloid-like fibrils than wild-type Abeta. Non-fibrillar Abeta(x-42) deposits precede the appearance of fibrils and the deposition of Abeta(x-40) in the vascular basement membrane. CAA severity tends to increase with age but may vary greatly among patients of comparable ages. Lumenal narrowing of affected blood vessels, leukoencephalopathy, CAA-associated vasculopathies, and perivascular astrocytosis, microgliosis, and neuritic degeneration complicate the development of HCHWA-D CAA. Parenchymal Abeta deposition is also enhanced in the HCHWA-D brain with non-fibrillar membrane-bound Abeta(x-42) deposits evolving into relatively fibrillar diffuse plaques variously associated with reactive astrocytes, activated microglia, and degenerating neurites. Plaque density tends to decrease with age. Neurofibrillary degeneration is absent or limited. HCHWA-D dementia is associated with CAA severity independently of Braak stage, age, and plaque density. Particularly, microaneurysms may contribute to the development of (small) hemorrhages/infarcts and the latter to cognitive decline in affected subjects. However, the relative importance of cerebral hemorrhages/infarcts, white matter damage and/or other CAA- or Abeta-related factors for cognitive deterioration in HCHWA-D remains to be determined.
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PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type. 1638 77