Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002395 (Alzheimer's disease)
 110,584 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 1400 necropsies performed on patients with either a nontraumatic cerebral hemorrhage (400 cases) or with dementia over the age of 55 (1010 cases), or both, have been reviewed. There were 15 cases in which a cerebral hemorrhage had occurred together with cerebral amyloid angiopathy all of whom had been demented. Eight of the 15 patients were hypertensive. The 7 non-hypertensives showing only the amyloid change included two cases of "atypical" Alzheimer's disease with acute neurological features, and 5 cases of senile dementia (aged 72 to 78 years) coupled with focal neurological disorders. In the hypertensive patients, aged 67 to 86 years, with a progressive dementing syndrome and acute neurological signs, multiple ball-like hemorrhages (7 cases) and/or cerebral hematomas (3 cases) were associated with a combination of amyloid and hyalinar (hypertensive) angiopathy, often affecting segments of the same pial and cortical vessels. From these data and recent reports on lethal cerebral hemorrhage occurring spontaneously or after neurosurgical procedures in demented old people, cerebral amyloid angiopathy, which is not necessarily associated with systemic amyloidosis or severe (pre)senile cerebral degeneration, may be considered a rare but important cause of cerebral hemorrhage in the aged. The "vascular" type of presenile dementia, occasionally complicated by focal cerebrovascular lesions or bleeds, is considered a variant of Alzheimer's disease. The mechanism leading to formation of cerebral amyloid is unknown.
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PMID:Cerebrovascular amyloidosis with cerebral hemorrhage. 6 54

1. All essential attributes of the amyloidosis in aged persons ("senile amyloidosis") correspond to the condition which in younger individuals develops after infections, particularly following tuberculosis and lymphogranulomatosis, as so-called secondary amyloid degeneration, and also manifests many features of the so-called primary amyloidosis, not connected with infections. 2. Amyloid depositions in the brain, cardiac muscle, and in pancreatic islets (the "senile amyloidotic triad") dominate the morbid anatomic aspect. However, we know no organ or tissue which necessarily remains spared. The number of involved organs and tissues, in general, increases with the progressive aging of the patients. In those persons living long enough, amyloidosis affects every individual and probably all organs and tissues. 3. Contrary to the so-called secondary amyloidosis, in many cases of senile amyloidosis the spleen, liver and kidney remain intact. 4. In the so-called Alzheimers disease, in which both clinically and pathoanatomically a particularly destructive cerebral amyloidosis in relatively young persons prevails, just as in the common senile dementia of aged persons, the brain condition is associated with a systemic amyloid degeneration of many other organs. 5. Several cerebral and cardiac lesions due to amyloid accumulations can probably be diagnosed electrographically. Thus, through these already known morbid anatomical observations we have the promise of an essential enrichment of diagnostic perspectives. 6. In general, the etiologic manifoldness of amyloidosis presently seems to be incomparable. Infections, ionizing radiation, traumatic lesions in human pathology, the introduction of chemically definable substances, infections, and stress consequent to social burdening, proved effective in spontaneous and experimental amyloid degeneration of animals. 7. The demonstration of a tuberculous infection with the help of postmortem radiographs, as well as with the employment of histologic and microbiologic procedures to provide the evidence of acid fast bacilli in calcified remnants of pulmonary foci, proved to be eminently successful methods in the exploration of causes of senile tuberculosis and amyloidosis: Tuberculosis, after its invasion of the organism in early childhood, with its toxic and immunobiologic influences, holds it under its spell for an entire, even very long life and can be considered the most frequent cause of senile amyloidosis. 8. Chromosomal disturbances, with their hereditary manifestations, or, as in cases of mongoloid idiocy, associated with individual deformations, may present as amyloidoses. 9. Amyloid deposits in human pathology may develop by the transformation of normal structures, like cartilage, osteoid tissue, vascular elastic fibers, and also from scar hyalin and from fibrin. 10. We observed the disappearance of cerebral and cardiac amyloid accumulations producing typical defects. 11. Amyloidosis represents one of the most frequent spontaneous diseases of animals...
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PMID:[Amyloidosis as a manifestation and origin of presenile and senile degeneration]. 13 66

In three cases of cerebral amyloid angiopathy there was also a chronic cerebral vasculitis characterized by segmental fibrinoid necrosis, chronic adventitial inflammatory infiltrates, obliterative "endarteritis" and hyaline arteriolar change, resembling rheumatoid vasculitis. Two of these cases had rheumatoid arthritis, and one had unspecified "arthritis" at the onset of dementia. Both vasculitis and amyloidosis involved the leptomeningeal and cerebral cortical vessels. In the two autopsy-verified cases, the vascular disease was limited to the brain. In the third case, only a brain biopsy was available. Amyloid-containing neuritic plaques were present in the cerebral cortex in all three cases, but they were abundant only in one, which also showed numerous Alzheimer tangles.
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PMID:Cerebral amyloid angiopathy: possible relationship to rheumatoid vasculitis. 57 77

Primary cerebrovascular amyloidosis resulting in significant cerebral parenchymal damage was encountered in 23 autopsied cases at the Mayo Clinic over the past 10 years. Patients were 60 to 97 years old and both sexes were equally represented. Large- and medium-sized leptomeningeal and cortical arteries showed the characteristic pattern of medial and intimal involvement, with luminal stenosis. The walls of smaller arteries were often diffusely infiltrated, with fibrinoid degeneration and miliary aneurysm formation. The amyloid nature of the infiltrate was confirmed by electron microscopic examination in all cases. All cases showed varying numbers of perivascular or independent senile plaques in the cerebral cortex. Alzheimer's neurofibrillary tangles were absent or were limited to the hippocampal region in all but two cases. Multiple, small cortical infarcts and hemorrhages were regularly present. Larger hemorrhage was present in nine cases. Of nine patients with terminal massive cerebral hemorrhage, only two were hypertensive. Six patients had had progressive dementia; four had had single episodes of vascular events and seven, multiple episodes; and four had had both dementia and vascular episodes. Primary cerebral amyloid angiopathy should be regarded as an important cause of mental deterioration and fatal cerebrovascular accidents in the elderly.
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PMID:Clinicopathologic studies of primary cerebral amyloid angiopathy. 75 33

New historic, morphologic, localisatory, chemical, etiological and pathogenetical observations urge the revision of problems of the so-called amyloidosis and suggest a new logical terminology. Cerebral amyloidosis, which corresponds to the clinical picture of senile dementia and Alzheimer's disease, is the local manifestation of a generalized systemic degeneration typified by amyloidotic deposits in aged persons. Chronic lingering tuberculosis, traumatic cerebral injury, genic aberrations, ionising radiations as well as a chronic "slow" virus infection (in cases of Creutzfeldt-Jakob's disease) proved to be inducers of cerebral amyloid deposits. Glenner and his associates succeeded in transforming Bence-Jones albumin into amyloid in vitro. The present writer observed the direct development of amyloid from vascular elastic fibers, from the ground substance of cartilage and osteoid tissue, and from fibrin. Regression of cerebral, cardiac and hepatic amyloid deposits occurs. Similarities between electron microscopic structures bring about difficulties in the morphologic definition of amyloid and cause tinctorial and ultramicroscopic resemblances between cellulose, amyloid and certain vira, although they represent chemically and biologically different materials.
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PMID:[Amyloidosis, expression and cause of presenile and senile mental and physical regression. A revision of the amyloid problem (author's transl)]. 121 Aug 40

beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitors (PPI) are a broad family of glycoproteins with the function of eliminating unwanted proteolysis of serine proteases. Their role in amyloidogenesis has become a subject of intense discussion, especially since the recent identification of alpha 1-antichymotrypsin in the beta-protein amyloid deposits of Alzheimer's disease. We evaluated immunohistochemically and biochemically the presence and distribution of several PPIs (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-macroglobulin and tissue inhibitor metalloproteinase) and amyloid P component in A beta 2M deposits in osteo-articular and visceral tissues from dialysis patients with amyloidosis, as well as two carpal tunnel synovia from non-dialysis patients and one Alzheimer's brain as controls. The immunohistochemical study demonstrated that all but one (anti-alpha 1-antichymotrypsin) of the PPI antibodies tested showed varying degrees of positive reaction against A beta 2M deposits. All the antibodies (including anti-alpha 1-antichymotrypsin) also reacted to some extent with other non-amyloid visceral and connective tissue elements diffusely and/or selectively. Among them, only the reaction of anti-amyloid P component had significantly distinctive localization to A beta 2M deposits, which were identified in adjacent serial sections by Congo red staining and immunohistochemical reaction against anti-beta 2m.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Demonstration of plasma proteinase inhibitors in beta 2-microglobulin amyloid deposits. 128 Jul

Abnormal proteolytic processing of amyloid precursor protein (APP) is thought to be central to the formation and deposition of beta amyloid peptide in Alzheimer's disease. A putative "secretase" activity normally releases an amino-terminal APP fragment by cleaving APP at residues within the beta amyloid peptide thereby precluding amyloidogenesis. In order to better understand the requirements for APP cleavage by secretase, we have expressed a modified cDNA construct representing the 751-amino acid isoform of APP (APP-REP) and mutated APP-REP proteins in cultured cells. Here, we show that: (a) APP-REP is predominantly associated with membranes; (b) intracellular turnover and processing of APP-REP is similar to that reported for the intact APP protein; (c) secretion appears unaltered by introduction of the glutamate to glutamine mutation found in the APP gene of patients suffering from hereditary cerebral hemorrhage with amyloidosis of Dutch origin; (d) a mutation in which the 18 juxtamembranous amino acids encompassing the secretase site are deleted also allows release of an amino-terminal fragment into the conditioned medium; and (e) kinetics of cleavage of APP-REP and its mutated derivatives are similar. These results indicate that the secretory cleavage of the extracellular amino-terminal fragments of APP-REP can occur in the presence of different novel juxtamembranous amino acid sequences.
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PMID:Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells. 128 Nov 62

Cerebral hemorrhages with amyloidosis and dementia of the Alzheimer type have many neuropathological findings in common, but there are also marked quantitative and qualitative differences. That makes it highly improbably that the B-protein amyloid depositions itself are the direct cause of extensive neuronal death and dementia in DAT.
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PMID:Neuropathological findings in cerebral B-protein amyloidosis. Differences and similarities in those cases presenting as a cerebral hemorrhage and those presenting as a dementia of the Alzheimer type. 132 May 18

In 11 of 11 inclusion-body myositis (IBM) patients, including one hereditary case, vacuolated muscle fibers contained large and multiple small inclusions immunoreactive for beta-amyloid protein (beta AP). All IBM muscle biopsies had characteristic cytoplasmic tubulo-filaments (CTFs) by electron microscopy. None of 14 control muscle biopsies contained the beta AP immunoreactive (IR) inclusions characteristic of IBM. On the light microscopy level, beta AP-IR inclusions colocalized with ubiquitin immunoreactivity. By immunogold electronmicroscopy, beta AP immunoreactivity was localized to a) amorphous, poorly defined structures, b) dense floccular material, c) clusters of loosely packed amyloidlike fibrils 6-8 nm in diameter, and d) poorly defined loose fibrillar structures 6-8 nm in diameter. beta AP immunoreactive structures were often in proximity to CTFs, but CTFs themselves never contained beta AP-IR. Our study provides the first demonstration of beta AP accumulations in abnormal human muscle. This finding suggests that in addition to Alzheimer's disease, Down syndrome, and Dutch-type hereditary cerebrovascular amyloidosis, beta AP may play an important role in the pathogenesis of other diseases, including ones outside the central nervous system, for example, IBM.
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PMID:Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis. 132 64

Tris-HCl or Laemmli sample buffer extracted frontal lobe and hippocampal samples from normal aged and Alzheimer's disease (AD) subjects were used to determine total ubiquitin (Ub), distribution of monomeric Ub and Ub-protein conjugates and amyloid enhancing factor (AEF) activity using the dot-blot, Western blot and mouse AEF bioassay techniques, respectively. The AD samples, as compared to the normals, demonstrated a 1.7-fold increase in total Ub, elevated levels of Ub-protein conjugates and an appreciably enhanced AEF activity. Many of the hippocampal Ub-protein conjugates were found to be soluble only in the Laemmli sample buffer. The possible roles of elevated Ub levels and of the association of AEF activity with Ub are discussed in regard to pathogenesis of brain amyloidosis.
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PMID:Ubiquitin profile and amyloid enhancing factor activity in Alzheimer and 'normal' human brain extracts. 132 64


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