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

To clarify the pathogenesis of cerebrovascular amyloid deposits, histological and immunocytochemical studies were performed on the central nervous system (CNS) in ten cases with type I familial amyloid polyneuropathy (FAP). They commonly suffered from peripheral somatic and autonomic nerve disorders without any CNS dysfunctions. However, all cases showed CNS amyloid deposits, mainly on the leptomeningeal vessels and pia-arachnoid membranes, with arteries and arterioles in the subarachnoidal space being the predominant site of cerebral amyloid accumulation. Using immunocytochemical staining methods with antibodies to amyloid beta-protein, human cystatin C and transthyretin (prealbumin), all of these amyloid deposits were specifically immunolabeled by the anti-human transthyretin antibody. However, there was no transthyretin-related amyloid deposits in the brain parenchyma. It is concluded that CNS transthyretin-immunoreactive amyloid deposition with cerebral amyloid angiopathy (CAA) is a common pathological finding in this disease. Moreover, the patients with type I FAP are known to have an amyloid protein precursor (a variant of transthyretin) in serum. This transthyretin type of CAA, therefore, seems to be an example of cerebrovascular amyloid deposits derived from a serum precursor.
 ...
PMID:Transthyretin-type cerebral amyloid angiopathy in type I familial amyloid polyneuropathy. 185 83

Analysis of the pathology of multi-infarct dementia is best carried out using a two-axis approach. The first axis describes the tissue damage, classified as macroinfarcts, cortical microinfarcts, basal ganglionic lacunes, white matter lacunes, dilated perivascular spaces, diffuse white matter rarefaction, and perivascular edema. The second axis describes the vascular abnormalities, classified as atherosclerosis involving the extracranial or intracranial arteries, arteriolosclerosis, congophilic angiopathy, emboli, and no structural abnormality. Multiple infarcts and white matter rarefaction are commonly seen as a component of Alzheimer disease, in keeping with the development of congophilic angiopathy and possibly other vascular changes in the latter disease. Evidence is presented to support the concept that the white matter rarefaction of Alzheimer disease and aging is associated with perivascular edema, rather than partial infarction.
 ...
PMID:The pathological basis of multi-infarct dementia. 205 11

A monoclonal antibody (HK-249) that recognizes a glucosamine sulfate alpha 1----4 glucuronic acid-containing determinant in heparan sulfate (HS) chains of a basement membrane-derived heparan sulfate proteoglycan identified and immunolocalized HS specifically to the amyloid deposits in neuritic plaques (NPs), congophilic angiopathy (CA), as well as in neurofibrillary tangles (NFTs) and non-tangle-bearing neurons in the brains of Alzheimer's and Down's syndrome (DS) patients. Ultrastructural immunohistochemistry demonstrated that HS within neurons of Alzheimer's disease (AD) brain was localized to lipofuscin granules, an aging pigment previously shown also to contain beta-amyloid protein (BAP). Heparan sulfate also was localized to neurite-containing, nonfibrillar 'primitive' plaques that also demonstrated positive BAP immunoreactivity in both AD and DS brains. Antibodies to laminin, fibronectin, and a chondroitin sulfate proteoglycan failed to show positive immunostaining of the HS-containing sites described above. Analysis of DS patients at different ages revealed that HS accumulated within neurons of the hippocampus and amygdala as early as 1 day after birth. Young age-matched controls did not demonstrate similar positive HS immunoreactivity in neurons, whereas positive immunostaining for HS was observed in other regions thought to normally contain HS. The earliest deposition of BAP was first observed as 'amorphous' or 'diffuse' cortical deposits in DS brain in patients aged 18 and 24 years before the accumulation of fibrillar amyloid (observed in DS patients who are 35 years and older). These cortical deposits also contained positive HS immunoreactivity, implying that HS accumulation in conjunction with the BAP is an early event that ultimately may contribute to the early age-related accumulation (ie, as early as 35 years of age in DS) of NPs, NFTs, and/or CA. Furthermore the colocalization of HS and BAP in a number of specific locales in AD and DS brain indicates a possible interaction between these two macromolecules that may be important in lesion development in these two diseases.
 ...
PMID:Early accumulation of heparan sulfate in neurons and in the beta-amyloid protein-containing lesions of Alzheimer's disease and Down's syndrome. 214 82

Alzheimer's disease is the most common cause of progressive intellectual failure in aged humans. The filamentous brain lesions which define the disease occur within neurons (neurofibrillary tangles), in extracellular cerebral deposits (amyloid plaques) and in meningocerebral blood vessels (amyloid angiopathy). They are found in lesser numbers in the brains of virtually all old humans. A protein with a relative molecular mass (Mr) of approximately 4,000, designated amyloid beta-protein or amyloid A4 protein, is the subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease, normal ageing and trisomy 21 (Down's syndrome). The amyloid beta-protein is a small fragment of a membrane-associated glycoprotein, encoded by a gene on human chromosome 21 which is telomeric to a genetic defect that causes at least some cases of familial Alzheimer's disease. Until now, the pathological lesions of the disease have been found only in the brain, although reports of phenotypic abnormalities in non-neural tissues have suggested that Alzheimer's disease may be a widespread, systemic disorder. Here we report the detection of amyloid beta-protein deposits in non-neural tissues and blood vessels of Alzheimer's disease patients, including skin, subcutaneous tissue and intestine. The protein was also present in non-neural tissues in a proportion of aged, normal subjects. Our findings indicate that a principal feature of the disease process is expressed subclinically in tissues other than brain. The occurrence of amyloid beta-protein deposits in multiple tissues suggests that the protein may be produced locally in numerous organs or may, as in other human amyloidoses, be derived from a common circulating precursor. These observations affect the rationale for many experiments analysing the amyloid beta-protein precursor and its messenger RNAs in Alzheimer's disease brain tissue and have major implications for the pathogenesis and treatment of the disease.
 ...
PMID:Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease. 252 96

We report the clinical and neuropathological manifestations of Alzheimer's disease (AD) in nine kindreds of German ancestry all originating from the same two adjacent villages on the West bank of the Volga River. There have been 89 known demented persons (53 male, 36 female). Mean age of onset is 57.6 +/- 8.4 years with a range of 40 to 84. Mean age at death is 66.5 +/- 7.6 years with a range of 50 to 80. Mean disease duration is 10.3 +/- 4.8 years with a range of 3 to 23. Detailed medical records were available on 50 individuals. Of these, 24% had a seizure, 72% language disturbance, 36% rigidity, 16% tremor and 12% myoclonus. There were 15 autopsies on demented persons from 6 of the kindreds. One brain suggested Creutzfeldt-Jakob disease (CJD) in a woman with the typical clinical course. The remaining 14 brains showed typical neuropathological characteristics of AD including neuritic amyloid plaques, neurofibrillary tangles, amyloid angiopathy and granulovacuolar change. Amyloid plaques were also seen in the cerebellum in all but one brain in which this region was available for review. Autopsy material from five brains in four families has been stained with antibody directed against the amyloid peptide; in all cases, the neuritic plaques stained positively. Many of the families share common surnames. It is likely that these Volga German kindreds carry the same genetic mutation leading to Alzheimer's disease; and thus, they are a valuable resource for genetic investigations of AD. Thus far, the disease in these kindreds does not show close linkage to either the D21S1 or beta amyloid gene loci on chromosome 21.
 ...
PMID:Characteristics of familial Alzheimer's disease in nine kindreds of Volga German ancestry. 260 19

The beta-protein, a small fibrillar peptide which is the main constituent of the amyloid deposits in senile neuritic plaques and congophilic angiopathy derives by proteolytic cleavage from at least one of three large precursor proteins of 695 to 770 amino acids encoded by a gene on chromosome 21. In the brain the mRNA coding for these predicted proteins has been localized to neurons and non-neuronal cell types. Monoclonal antibodies raised to a synthetic peptide corresponding to residues 1 to 24 of the beta-protein do not only stain the amyloid deposits characteristic for Alzheimer neuropathology, but also neuronal lipofuscin. This material is immunoreactive in every brain area examined (cerebral and cerebellar cortices, basal ganglia, brainstem) and its reactivity is independent from the presence of Alzheimer's disease. At the ultrastructural level immunoreactivity is associated with the proteinaceous matrix part of lipofuscin which does not contain any fibrillar structures. Western blotting of a lipofuscin enriched fraction shows a beta-protein immunoreactive polypeptide migrating at approximately 31 kDa position on SDS-polyacrylamide gel electrophoresis. These results suggest that a large fragment of the amyloid precursor protein (approximately 280 residues) is associated with lipofuscin. Unlike in the microglial cell where the amyloid precursor is processed in a manner to release the beta-protein which forms amyloid fibers, one pathway of its physiological breakdown in the nerve cell seems to yield a large fragment which accumulates on a lipopigment characteristic for normal aging.
 ...
PMID:A 31 kilodalton beta-protein immunoreactive polypeptide in neuronal lipofuscin. 269 Jan 28

Central white matter lucencies are commonly seen in CT scans of elderly patients. Reports in the literature have implicated demyelination due to subcortical vascular disease (Binswanger disease) as the cause of these lucencies. Binswanger disease, however, is thought to be rare. Because of this apparent discrepancy we decided to determine the incidence and to attempt to define the clinical significance of the CT white-matter changes in a study population at New York University Medical Center. The studies of 275 normal and demented subjects, ages 23 to 85 years, were reviewed. All subjects received neurologic, psychiatric, and medical evaluation, formal psychometric evaluation of their cognitive status, and a CT scan. CT scans were evaluated for the presence and severity of white-matter changes (leukoencephalopathy). The incidence and severity of white-matter changes increased significantly with age (p less than 0.01). Leukoencephalopathy was consistently more common in demented patients than in normal subjects, but the difference was not statistically significant, and the severity of the leukoencephalopathy was not related to the severity of dementia (p less than 0.05). Five patients (ages 74 to 95 years) with a clinical diagnosis of Alzheimer disease who had CT evidence of lucencies were examined at autopsy. Neuropathology demonstrated extensive changes of Alzheimer disease in one brain and mild-to-moderate changes in the other four brains; areas of white-matter rarefaction were present in all brains, with microscopic evidence of arteriolar hyalinization. This study demonstrates that leukoencephalopathy is strongly related to the aging process and is seen in both "normal" and cognitively impaired individuals who have no other evidence of vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies. 308 33

We have purified and characterized the cerebral amyloid protein that forms the plaque core in Alzheimer disease and in aged individuals with Down syndrome. The protein consists of multimeric aggregates of a polypeptide of about 40 residues (4 kDa). The amino acid composition, molecular mass, and NH2-terminal sequence of this amyloid protein are almost identical to those described for the amyloid deposited in the congophilic angiopathy of Alzheimer disease and Down syndrome, but the plaque core proteins have ragged NH2 termini. The shared 4-kDa subunit indicates a common origin for the amyloids of the plaque core and of the congophilic angiopathy. There are superficial resemblances between the solubility characteristics of the plaque core and some of the properties of scrapie infectivity, but there are no similarities in amino acid sequences between the plaque core and scrapie polypeptides.
 ...
PMID:Amyloid plaque core protein in Alzheimer disease and Down syndrome. 315 21

As a comparison to previous analyses of purified amyloid plaque cores from Alzheimer's disease (AD) brain, we performed protein chemical and immunocytochemical studies on amyloid filaments extracted from meningeal blood vessels of patients with Alzheimer's disease. Results were compared with those obtained from identically prepared fractions of aged normals without cerebral amyloid angiopathy or other microscopic findings of AD. The amyloid isolation method of Glenner and Wong was modified, including an extraction with sodium dodecyl sulfate (SDS). Gel electrophoresis of purified amyloid from AD meninges yielded bands centered at 4.2 kDa. Sequencing of the HPLC-purified amyloid protein from AD meninges confirmed the published beta-protein sequence for residues 1-30 and 35-40, with the exception of glutamic acid rather than glutamine at position 11. N-terminal heterogeneity was not prominent. No sequence beyond residue 40 was obtained. Proteins of similar but not identical mol. wt. were present in HPLC-purified fractions of normal meninges; neither the beta-protein sequence nor any other interpretable sequence was detected in such fractions. Two antisera raised against the purified AD meningovascular amyloid protein identified the 4.2 kDa band on Western blots of AD preparations; no protein band in this region was labeled in control preparations. The 4.2 kDa band in AD meningeal preparations was also lableled by an antiserum to synthetic beta-peptide but not by an antiserum to the carboxyl terminus of the beta-protein precursor. Both the AD meningovascular amyloid antisera selectively labeled amyloid in cortical and meningeal vessels and plaque cores; tangles, plaque neurites, and cells of normal CNS and numerous non-neural tissues were unstained. The antisera also labeled the occasional deposits of vascular amyloid and less frequent plaque core amyloid found in some aged individuals without AD. We conclude that (1) the meningovascular amyloid beta-protein of AD, whose sequence has been confirmed and extended to residue 40, was not immunocytochemically detectable in neurofibrillary tangles; (2) beta-protein could not be detected in meningeal preparations from aged controls who lack light microscopically visible meningovascular amyloid; and (3) the vascular and plaque core amyloid present in aged normals is antigenically cross-reactive with AD meningovascular amyloid.
 ...
PMID:Protein chemical and immunocytochemical studies of meningovascular beta-amyloid protein in Alzheimer's disease and normal aging. 321 3

A polyclonal antibody to a 28 residue synthetic peptide, homologous to the NH2 terminal region of amyloid beta-protein, was employed in a study of the frontal and temporal cortex of 8 Alzheimer patients and 13 non-demented individuals aimed to define the relationship of immunolabelled to argyrophilic, congophilic and thioflavine S-positive cortical lesions. In Alzheimer patients, this antiserum labelled not only senile plaques and congophilic angiopathy, but also cortical deposits that were neither argyrophilic, congophilic nor thioflavine S-positive and were unrelated to degenerating neurites, tangle-bearing neurons or congophilic angiopathy. Similar lesions were observed in 4 of 13 non-demented individuals, in the absence of tangles, plaques or congophilic angiopathy, and in one in association with plaques. Such deposits might have been due to amyloid precursors still lacking the beta-pleated sheet molecular conformation responsible for amyloid tinctorial and optical properties.
 ...
PMID:Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. 324 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>