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)

The relationship between cognitive deterioration and abnormalities detected by magnetic resonance imaging (MRI) was investigated to determine the radiological correlates of cognitive deterioration in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). Twenty HCHWA-D subjects (12 patients who had suffered one or more strokes and eight who had not suffered a stroke) were studied with MRI and underwent extensive neuropsychological examination. On MRI the number of focal lesions was counted, and white matter hyperintensities (WMHs) were scored semiquantitatively. A significant correlation between cognitive deterioration and WMH score and number of focal lesions was found. However, cognitive deterioration, WMH score, and the number of focal lesions all increase with age, and therefore their mutual correlation can be explained as an age effect. This study shows that cognitive deterioration in HCHWA-D is not correlated with abnormalities detected by MRI (number of focal lesions and subcortical WMHs) independently of age. Although a contribution of white matter changes and/or focal lesions, possibly in combination with age, to cognitive deterioration cannot be excluded. Cognitive deterioration in these HCHWA-D patients is probably primarily the result of chronic damage of amyloid angiopathy to the brain, to which may be superimposed cognitive impairment from focal cerebral hemorrhage or infarction.
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PMID:Hereditary cerebral hemorrhage with amyloidosis-Dutch type: better correlation of cognitive deterioration with advancing age than with number of focal lesions or white matter hyperintensities. 893 82

Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor cognitive impairment may occur. In histological and immunohistochemical studies of the central nervous system in 4 patients with a G654A gelsolin mutation, we found widespread spinal, cerebral, and meningeal amyloid angiopathy, with deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1-antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular fibrinogen immunoreactivity was occasionally noted. The patients showed posterior column degeneration and diffuse loss of myelin in the centrum semiovale with perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1 patient, showed white matter lesions, colocalizing with the histological abnormalities. Our study shows that deposition of AGel in the spinal and cerebral blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia is an essential feature of this form of systemic amyloidosis and may contribute to the central nervous system symptoms.
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PMID:Gelsolin-related spinal and cerebral amyloid angiopathy. 1007 44

We observed two families with a dominantly inherited complex neurological syndrome with onset in adulthood. Family F included 9 affected in four generations. One patient showed prominent anticipation of onset age. Onset was with cerebellar signs followed by dementia, psychiatric symptoms, seizures, and extrapyramidal features. Family M included 14 affected individuals in five generations. Presenting symptoms were either psychiatric and cognitive impairment or a cerebellar syndrome. Extrapyramidal features, dysphagia, incontinence, seizures, and myoclonus may occur. In both families magnetic resonance imaging showed marked atrophy of the brain and cerebellum. Molecular analyses demonstrated an expanded CAG/CAA repeat in the in the TATA box-binding protein (TBP) gene (SCA17).
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PMID:Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17. 1459 69

We review accumulating evidence that cerebrovascular amyloid deposition (cerebral amyloid angiopathy [CAA]) is an independent risk factor for cognitive dysfunction. The two population-based autopsy studies that have analyzed cognitive status during life as a function of CAA have each suggested deleterious effects of CAA on cognition even after controlling for age and Alzheimer disease pathology. We also review data from patients with CAA-related intracerebral hemorrhage (the one form of CAA that can be noninvasively recognized) suggesting associations of CAA with radiographic white matter abnormalities and cognitive impairment. These data highlight the importance of elucidating the effects of vascular amyloid on cerebrovascular function and of developing therapeutic strategies for this potentially widespread form of microvascular cognitive impairment.
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PMID:Amyloid angiopathy-related vascular cognitive impairment. 1545 38

Previous findings demonstrated that haplotype B of CST3, the gene coding for cystatin C, is a recessive risk factor for late-onset Alzheimer's disease (AD; Finckh, U., von der Kammer, H., Velden, J., Michel, T., Andresen, B., Deng, A., Zhang, J., Muller-Thomsen, T., Zuchowski, K., Menzer, G., Mann, U., Papassotiropoulos, A., Heun, R., Zurdel, J., Holst, F., Benussi, L., Stoppe, G., Reiss, J., Miserez, A.R., Staehelin, H.B., Rebeck, G.W., Hyman, B.T., Binetti, G., Hock, C., Growdon, J.H., Nitsch, R.M., 2000. Genetic association of the cystatin C gene with late-onset Alzheimer disease. Arch. Neurol. 57, 1579-1583). In the present multicentric electroencephalographic (EEG) study, we analyzed the effects of CST3 haplotypes on resting cortical rhythmicity in subjects with AD and mild cognitive impairment (MCI) with the hypothesis that sources of resting EEG rhythms are more impaired in carriers of the CST3 B haplotype than non-carriers. We enrolled a population of 84 MCI subjects (42% with the B haplotype) and 65 AD patients (40% with the B haplotype). Resting eyes-closed EEG data were recorded in all subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Results showed that the amplitude of alpha 1 (parietal, occipital, temporal areas) and alpha 2 (occipital area) was statistically lower in CST3 B carriers than non-carriers (P < 0.01). Whereas there was a trend towards statistical significance that amplitude of occipital delta sources was stronger in CST3 B carriers than in non-carriers. This was true for both MCI and AD subjects. The present findings represent the first demonstration of relationships between the AD genetic risk factor CST3 B and global neurophysiological phenotype (i.e., cortical delta and alpha rhythmicity) in MCI and AD subjects, prompting future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.
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PMID:Genotype (cystatin C) and EEG phenotype in Alzheimer disease and mild cognitive impairment: a multicentric study. 1621 53

Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
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PMID:Cystatin C and subclinical brain infarction. 1623 9

Cerebral amyloid angiopathy is characterized by deposition of amyloid in the walls of leptomeninged and cerebral blood vessels. Its most common form, sporadic CAA that results from deposition of beta-amyloid peptide, which is the subject of this short review, is present in virtually all cases of Alzheimer disease and is also common among non-demented subjects where its prevalence increases with age. Stroke due to massive cerebral lobar hemorrhage is the main clinical presentation of CAA, but transient neurologic symptoms due to microhemorrhages may also occur. CAA is also a risk factor for cerebral infarction and there is increasing evidence that CAA contributes to cognitive impairment in the elderly, usually in association with white matter abnormalities on imaging. Although the definitive diagnosis of CAA is neuropathologic, reliable diagnosis can be reached clinically, based on the occurrence of strictly lobar hemorrhages, particularly in the cortico-subcortical area when using gradient-echo or T2*-weighted magnetic resonance imaging. Experimental studies have shown that the origin of the vascular amyloid is neuronal, and that age-related degenerative changes in the vessel walls prevent its clearance from the brain along perivascular spaces and promote Abeta aggregation and CAA formation. The entrapped Abeta aggregates are toxic to various vascular wall components, including smooth muscle cells, pericytes and endothelial cells, leading to their eventual destruction and predisposition of the vessel wall to rupture and hemorrhage. However, more research is necessary to decipher the mechanism of CAA formation and its relation to cognitive decline in the elderly.
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PMID:Cerebral amyloid angiopathy--a disease or age-related condition. 1718 Aug 35

Cerebral amyloid angiopathy (CAA) is characterized by deposition of cerebrovascular amyloid protein in the media of leptomeningeal vessels. (amyloid B protein, cystatin C, transthyretin, gelsolin, and prion protein). It is a cause of cerebrovascular disorders including cerebral hemorrhage, cognitive impairment and unusually transient neurological symptoms. It is the main contributing factor to cerebral hemorrhage after hypertension in the elderly. We aimed to review epidemiological, pathophysiological and clinical and MRI imaging data in CAA.
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PMID:[Cerebral amyloid angiopathy]. 1730 82

Accurate renal function measurement is important for identification of chronic renal disease which may allow early implementation of renoprotective therapy and proper medication dosing among elderly individuals. This paper proposed to review available data about the strengths and weaknesses of current methods of measuring and estimating of renal function and to appoint which of them is the best in older people. Serum creatinine and creatinine clearance are inaccurate screening tests for renal failure in elderly subjects leading to under-recognition and/or underestimation of the degree of renal failure due to the reduced muscle mass and the inappropriate collection of a timed urine sample (urinary incontinence, cognitive impairment). For all their limitations, formulaic estimates of glomerular filtration rate can provide better information in this population. Further researches must be focused on development of a more precise estimation equation and on implementation in clinical practice of a novel marker of renal function, serum cystatin C, claimed to be superior to plasma creatinine in the elderly individuals.
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PMID:[Assessing renal function in elderly people]. 1759 43

Whereas the prevalence and impact of vascular pathology in Alzheimer diease (AD) are well established, the role of vascular and Alzheimer pathologies in the progression of neurodegeneration and cognitive impairment in Parkinson disease (PD) is under discussion. A retrospective clinico-pathologic study of 100 patients with autopsy proven PD (including 44 cases with dementia/PDD) and 20 cases of dementia with Lewy bodies (DLB) confirmed essential clinical (duration of illness, Mini-Mental State Examination/MMSE, age at death) and morphologic differences between these groups; Lewy body Braak scores and Alzheimer pathologies (neuritic Braak stage, cortical Abeta plaque load, and generalized cerebral amyloid angiopathy or CAA) were significantly higher/more severe in DLB and PDD than in PD without dementia. Duration of illness showed no association to any of the examined pathologic parameters, while there was a moderate association between LB scores and neuritic Braak stages, the latter significantly increasing with age. Significant association between cerebrovascular lesions and neuritic Braak stage was seen in PDD but not in PD subjects without dementia. These data suggest an influence of Alzheimer-related lesions on the progression of the neurodegenerative process and, in particular, on cognitive decline in both PDD and DLB. On the other hand, both these factors in PD and DLB appear to be largely independent from coexistent vascular pathology, except in cases with severe cerebrovascular lesions or those related to neuritic AD pathology. Assessment of ApoE genotype in a small number of cases showed no significant differences in the severity of Abeta plaque load and CAA except for much lower intensities in non-demented epsilon3/3 patients. Despite increasing evidence suggesting synergistic reactions between alpha-synuclein (alphaSyn), tau and Abeta-peptides, the major protein markers of both AD and Lewy body diseases, and of both vascular pathology and AD, the molecular background and pathophysiological impact of these pathologies on the progression of neurodegeneration and development of cognitive decline in PD await further elucidation.
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PMID:Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. 1827 24


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