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)

Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.
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PMID:An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). 765 71

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer's disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.
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PMID:Epidemiology of vascular dementia. 1042 61

We have reported earlier that tight-junction proteins are detectable by standard immunohistochemistry in the brain parenchyma, namely in the cell bodies of neurons, astrocytes, and oligodendrocytes. Here we show, by projection to latent structures - discriminate analysis (PLS-DA), that the immunohistochemical detection profile of tight junction proteins clearly distinguishes the AD cases from healthy aging controls and from the cases of dementia with a predominantly vascular pathology underlying the symptoms (vascular dementia, VaD; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL; and cerebral amyloid angiopathy, CAA). Our findings might be valuable in the perspective of developing biomarkers for AD.
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PMID:Claudin expression profile separates Alzheimer's disease cases from normal aging and from vascular dementia cases. 2266 53

The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the 'ageing brain'. These include angiopathies (affecting both large and small arteries) that result from 'classical' risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD - though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects of CVD may include neuroinflammation and biochemical 'lesions' that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change - commonly seen in the brains of geriatric subjects - remains controversial. In recent years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL, Trex1-related microangiopathies, CARASAL, familial forms of cerebral amyloid angiopathy or CAA) have provided interesting cellular and molecular clues to the pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD-related CAA.
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PMID:Review: Vascular dementia: clinicopathologic and genetic considerations. 2938 Sep 13

Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used MEDLINE, EMBASE, and GOOGLE SCHOLAR to provide an extensive update about epidemiology, classifications, pathology, clinical findings, diagnostic tools, and treatments of leukodystrophies. Comprehensive evaluation of clinical findings, brain magnetic resonance imaging, and genetic studies play the key roles in the early diagnosis of individuals with leukodystrophies. No cure is available for most heritable white matter disorders but symptomatic treatments can significantly decrease the burden of events. New genetic methods and stem cell transplantation are also under investigation to further increase the quality and duration of life in affected population.Expert opinion: The improvements in molecular diagnostic tools allow us to identify the meticulous underlying etiology of leukodystrophies and result in higher diagnostic rates, new classifications of leukodystrophies based on genetic information, and replacement of symptomatic managements with more specific targeted therapies.Abbreviations: 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive.
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PMID:An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. 3182 48

Vascular cognitive impairment (VCI) refers to the entire spectrum of vascular brain pathologies that contribute to cognitive deficits, ranging from subjective cognitive decline to dementia. The main pathologies in VCI are infarcts and white matter hyperintensities due to ischemia. VCI rodent models can be divided into surgical models (e.g., MCAO, BCAO, BCAS, 2-VO, 4-VO) and genetic models (e.g., SHR/SP, T2DM, CAA, CADASIL) based on construction methods. However, no single model can fully recapitulate the pathogenesis of VCI, and choosing the appropriate model for different research purposes would be of crucial importance. Here, we have summarized the commonly used rodent VCI models and discussed their advantages and limitations to provide a necessary reference for selecting suitable animal models to investigate the molecular pathways involved in VCI and develop therapeutic interventions.
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PMID:Rodent Models of Vascular Cognitive Impairment. 3310 13