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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the immunocytochemical characteristics of the ballooned neurons (BN) in three patients with cortical degeneration with neuronal achromasia (CDNA) using antibodies to phosphorylated neurofilaments (PNF), tau, Alz-50, ubiquitin, beta (A4) amyloid, and glial fibrillary acidic protein. All BN exhibited intense perikaryal staining for PNF protein. Most BN and some normal-appearing neurons also stained for ubiquitin and Alz-50. The BN did not immunostain for tau protein, and none of the cases had tau-reactive neocortical neurofibrillary tangles or Pick bodies. One case had occasional senile plaques that stained for beta amyloid; no case had amyloid angiopathy. Our findings suggest that the pathophysiologic basis of the cortical degeneration in CDNA involves an alteration of neuronal cytoskeletal metabolism affecting neurofilament and possibly microtubular proteins in conjunction with activation of the ubiquitin proteolytic system.
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PMID:Immunocytochemical study of ballooned neurons in cortical degeneration with neuronal achromasia. 131 3

Immunohistological findings in cerebral blood vessels of 4 cases with cerebral amyloid angiopathy (CAA) were compared with those of 4 Alzheimer's (AD) cases. A panel of antibodies against 2 neurofilament subunits (BF10 and RT97), a microtubule-associated protein (TAU) and ubiquitin were used. CAA cases showed a strong immunoreactivity for ubiquitin in blood vessel wall. Senile plaques (SPs) in CAA cases showed strong ubiquitin positivity but the central amyloid core was negative. AD brains showed immunoreactivity with all antibodies in SPs and neurofibrillary tangles (NFTs); blood vessels were consistently negative for ubiquitin. Control brains showed few SPs and NFTs; these were positive for ubiquitin, but blood vessels were negative. These results indicate that vascular amyloid deposition in CAA and AD may have different pathophysiological mechanisms.
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PMID:Ubiquitin in cerebral amyloid angiopathy. 146 19

A 54-year-old man who had cerebellar ataxia and pseudobulbar palsy at the age of 29 years, and soon developed dementia, myoclonus and convulsions, died after about 20 years in a vegetative state. Histological examination of the extensively atrophic and devastated brain (680 g) revealed the almost total loss of cerebral cortical neurons associated with numerous beta-protein amyloid plaques, many extracellular tangles and a large number of hypertrophic astrocytes, and prominent amyloid angiopathy. The astrocytes were frequently immunopositive for anti-human tau antibody (anti-htau) and anti-ubiquitin antibody (anti-ubi). Double immunostaining with anti-htau and anti-glial fibrillary acidic protein (GFAP) antibody clearly demonstrated htau-positive domains within the GFAP-positive perikarya/and processes of several astrocytes. Electron microscopy of the hippocampal CA1, which was completely devoid of pyramidal neurons, revealed, in astrocytes, abnormal filaments indistinguishable from the paired helical filaments (PHFs) seen in neurons. On immunoelectron microscopy, the filaments were observed to be labeled with anti-htau and anti-ubi, exhibiting the same immunohistochemical features as neuronal PHFs. This is the first demonstration of clearly constricted and both tau- and ubiquitin-positive PHFs in astrocytes, indicating that, in some special conditions like in our case, processes similar to those that attack neurons also affect astrocytes and ultimately make the latter form PHFs.
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PMID:Paired helical filaments in astrocytes: electron microscopy and immunohistochemistry in a case of atypical Alzheimer's disease. 155 54

The cytoskeletal pathology of a patient with familial Alzheimer's disease (AD) associated with the probably causal amyloid precursor protein (APP) codon 717 Val----Ile mutation is described. In addition to moderately extensive beta A4 protein deposition within the substance of the brain and in blood vessel walls (congophilic angiopathy), there was abundant cytoskeletal pathology in the form of neurofibrillary tangles, plaque neurites and neuropil threads. Interestingly, plentiful cortical and subcortical Lewy bodies were also seen. In order to compare the cytoskeletal pathology in this case with that seen in sporadic cases of AD we (1) studied the immunohistochemical profile of the amyloid and cytoskeletal pathology with antibodies to beta A4 protein, tau, phosphorylated neurofilament epitopes and ubiquitin and (2) performed a biochemical fractionation and Western blot analysis for the abnormally phosphorylated form of tau (A68) characteristically seen in AD. No substantial difference between the familial case and sporadic cases could be found. We conclude that it is now reasonable to hypothesise that an abnormality in APP metabolism is responsible not only for the deposition of beta A4 protein, but also for the range of cytoskeletal pathology, typical of AD.
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PMID:Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology. 158 63

Senile plaques (SP) in the cerebellum of 23 cases of Alzheimer's disease (AD), three with widespread amyloid angiopathy, were studied with a modified Bielschowsky stain and immunocytochemical methods using antibodies to a beta-amyloid synthetic peptide (beta ASP), phosphorylated neurofilament proteins, ubiquitin, tau protein, and glial fibrillary acidic protein (GFAP). The four subtypes of SP (diffuse plaques, compact plaques, perivascular plaques, and subpial fibrillar deposits) that were observed with the modified Bielschowsky stain were also stained with antibodies to beta ASP. Many cerebellar SP contained ubiquitin-positive granular elements resembling dystrophic neurites. In contrast to neuritic elements in cerebral SP in AD, ubiquitin-positive elements in cerebellar SP were not labeled with antibodies to phosphorylated neurofilament or tau proteins. Various degrees of glial reaction were observed in all subtypes of SP except diffuse plaques. The absence of phosphorylated neurofilament and tau epitopes in neuritic elements in cerebellar SP is not surprising since paired helical filaments have not been seen in the cerebellum. Nevertheless, our results suggest that cerebellar SP are frequently associated with dystrophic neurites.
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PMID:Modified Bielschowsky and immunocytochemical studies on cerebellar plaques in Alzheimer's disease. 168 24

The nature of senile plaques (SP) in 27 cases of diffuse Lewy body disease (LBD) was investigated using immunocytochemistry and antibodies to beta amyloid protein synthetic peptides (BetaSP), ubiquitin (UBQ), paired helical filaments (PHF; Ab39) and a 68-kDa protein in Alzheimer brains (Alz50). Lewy bodies were present in widespread areas of the neocortex of all cases and were more easily detected with ubiquitin immunocytochemistry than with conventional stains. All cases had neocortical SP, but only six cases had neocortical neurofibrillary tangles (NFT). SP were very numerous in most cases and were usually "pale", "diffuse" or "very primitive" plaques with thioflavin S fluorescent microscopy. SP in diffuse LBD were immunostained with BetaSP. Several cases had extensive amyloid angiopathy that was also immunoreactive with BetaSP. SP in diffuse LBD were characterized by amyloid deposits with few or no neuritic elements that could be detected with thioflavin S, Bielschowsky's stain or double staining with BetaSP and Bodian's silver stain. They differed from plaques in Alzheimer's disease by lack of PHF-type neurites that could be stained with Ab39. In diffuse LBD, SP contained PHF-type neurites only in areas coexistent with NFT. Some SP had round, granular neurites that were immunoreactive with UBQ, but weakly argyrophilic with Bodian's stain and nonfluorescent with thioflavin S. Diffuse LBD lacked significant neuritic change in the neuropil that could be detected with UBQ, Ab39 and Alz50. The latter finding is a characteristic feature that distinguishes Alzheimer's disease from diffuse LBD.
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PMID:Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques. 268 63

To determine whether apolipoprotein E (APOE) genotype affects neuropathology in Lewy body disease (LBD), we examined 18 cases of LBD that did not have concurrent Alzheimer's disease by the CERAD criteria. We obtained APOE genotypes, determined diffuse beta-amyloid plaque (A beta P) and Lewy body densities in multiple brain regions, and graded the intensity of CA2-3 ubiquitin-positive neurites, vacuolar change, nigral pathology, amyloid angiopathy, and subpial amyloid deposition. The APOE allele frequencies were as follows: epsilon 2, 0.14 +/- 0.07; epsilon 3, 0.64 +/- 0.08; and epsilon 4, 0.22 +/- 0.03. The mean A beta P density was lower in APOE epsilon 3/3 cases (14.5 A beta Ps per mm2) than in the groups with the APOE epsilon 2 (67.0) or APOE epsilon 4 (46.6) alleles. This difference was due largely to the difference between A beta P density in the APOE epsilon 2 group and the APOE epsilon 3/3 group (F = 5.525, p < 0.02). CA2-3 neuritic degeneration was greater in those with the APOE epsilon 4 allele than in those with the APOE epsilon 3/3 genotype (grade = 1.9 +/- 1.3 versus 0.938 +/- 0.9; Kruskal-Wallis test statistic = 6.962, p < 0.05). These data are consistent with the hypothesis that APOE genotype may affect neuropathology in LBD.
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PMID:Apolipoprotein E genotype and Lewy body disease. 782 44

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

IBM has emerged as a clinicopathological entity during the past 25 years but with increasing complexity. It occurs primarily in elderly persons (over the sixth decade of life, with 3:1 male preponderance), but young adults or children may also be affected in some families. FIBM is by and large non-inflammatory though some autosomal dominant FIBM cases have inflammatory cell infiltrates. In IBM, slowly progressive weakness of proximal as well as distal muscle groups occurs and is usually not associated with skin rash or malignancy. The incidence of associated collagen-vascular disease is thought to be lower than in DM or PM but is reported to be as high as 15%. It is generally refractory to treatment with corticosteroids or other immunosuppressants. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. None of the histopathological features is specific enough to be a diagnostic criterion. The diagnostic criteria have to be collective, encompassing both clinical and pathological criteria in different combinations. The presence of eosinophilic intranuclear or cytoplasmic inclusions immunoreactive for both beta-amyloid and ubiquitin in affected myofibres may facilitate the diagnosis of IBM. The diagnosis no longer depends on the ultrastructural demonstration of characteristic microtubular filaments as previously thought. The identification of both beta-amyloid and ubiquitin may provide a new concept for the disease process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal amyloid protein in IBM is suspected to be similar to that in Alzheimer's disease. IBM is considered to be intimately related to a heterogenous group of non-inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and dominant FIBM. An inflammatory response has been seen, however, in muscles of both OPMD and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may not be the same. Unlike IBM, there is no abnormal sarcolemmal expression of MHC-I antigen in IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre destruction. The prion theory derived from identification of amyloidogenic protein in the filament inclusions in the rimmed vacuoles is provocative. If one believes in the contention that the amyloidogenic filaments are the primary pathogen of either IBM or IBMD, one must account for the fact that these filaments are originally derived from sarcolemmal nuclei and not from autophagic vacuoles. Until this is clarified, the possibility that the filaments represent either abnormal or defective 'slow' virus nucleocapsids cannot be completely ruled out.
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PMID:Inclusion body myositis. 815 43

In this study, we immunohistochemically examined the several constituents of senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in aged cynomolgus monkeys. Apolipoprotein E (apoE) deposited in all mature plaques and CAA, and in half of the diffuse plaques. Alpha-1-antichymotripsin (alpha ACT) deposited in half of the mature plaques and in one third of the CAA. Amyloid precursor protein (APP), ubiquitin (Ub), and microtubule-associated protein-2 (MAP-2) accumulated in the swollen neurites of mature plaques. Glial fibrillary acidic protein (GFAP) was detected in the astrocytes and their processes surrounding the mature plaques. Tau was detected in neither the SPs nor CAA. Therefore, mature plaques involved extracellular A beta, apoE, and alpha ACT, and also astrocytes and swollen neurites. However, diffuse plaques involved only extracellular A beta and apoE. Since these features, except for tau, were consistent with those in humans, this animal model will be useful for studying the pathogenesis of cerebral amyloid deposition.
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PMID:Immunohistochemical characteristics of the constituents of senile plaques and amyloid angiopathy in aged cynomolgus monkeys. 890 9


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