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)

Disorders of the central nervous system were found in 150 rats five monthds after en-to-side-porta-caval anastomosis consisting of vacuolisated cytoplasma of gangliacells and reactions of the glia comparable with the Alzheimer-glia-type II. Since these disorders are consistent with those in patients with liver cirrhosis but induced in these experiments by a porta-caval anastomosis alone, they are proposedly independent from liver disease itself. It is discussed whether disorders in glucose homeostai may be of pathogenetic relevance. Atrophy of tests, found in the late postoperative phase and erosions or ulcers of gastric mucosa as well as nephrolithiasis with hydronephrosis as consequence, the latter occuring independently from the time after operations, are proposedly due to the porta-caval anastomosis, too.
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PMID:[Morphological investigations of extrahepatic disorders after porta-caval end-to-side-anastomosis in rats (author's transl)]. 89 4

We previously suggested the hypothesis that defective neuronal plasticity is a major neurobiological deficit causing the dementia of Alzheimer's disease (AD). We used message levels of the growth-associated protein, GAP-43, as a marker of axonal plasticity to examine the hypothesis of defective neuronal plasticity in AD. When all AD cases are combined, the average level of GAP-43 message in area 9 of the AD frontal association cortex was not significantly different from the level in the comparably aged control cortex. Differentiation of AD cases on the basis of neurofibrillary tangle (NFT) density revealed that in AD cases with high tangle density average GAP-43 message level was reduced fivefold relative to levels in AD cases with low NFT density. AD cases with low neurofibrillary tangle density had levels of GAP-43 message that were not significantly different from the levels of normal controls. Differentiation of AD cases on the basis of neuritic plaque density did not indicate as strong a relationship to GAP-43 message level. The association between neurofibrillary tangle density and GAP-43 message level suggests the hypothesis that neurofibrillary tangles may reduce GAP-43 expression. Data of others show a relationship between high NFT density and reduced levels of synaptophysin-like immunoreactivity and reduced cerebral glucose metabolism. These data combine to suggest a set of AD cases with high NFT density, reduced axonal plasticity, reduced synaptic density, and reduced cerebral glucose metabolism--all variables that may be directly related to the functioning of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer's disease. 128 45

Brain capillary endothelium has a high density of the GLUT-1 facilitative glucose transporter protein. This is reasonable in view of the brain's high metabolic rate for glucose and its isolation behind unique capillaries with blood-brain barrier properties. Thus, the brain endothelium, which constitutes less than 0.1% of the brain weight, has to transport glucose for the much larger mass of surrounding neurons and glia. I describe here the changes that occur in the density of glucose transporters in brain capillaries of subjects with Alzheimer disease, where there is a decreased cerebral metabolic rate for glucose, and in a novel clinical entity characterized by defective glucose transport at the blood-brain barrier. In subjects with Alzheimer disease, cerebral microvessels showed a marked decrease in the density of the glucose transporter when compared with age-matched controls, but there was no change in the density of glucose transporters in erythrocyte membranes. Thus, I believe that the decreased density of glucose transporters in the brains of subjects with Alzheimer disease is the result rather than the cause of the disease. In contradistinction, the primary defect in glucose transport at the blood-brain barrier in subjects with the recently described entity is associated with decreased density of GLUT-1 in erythrocyte membranes.
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PMID:Changes in the glucose transporter of brain capillaries. 129 61

Aluminum accumulation has been implicated in the development of Alzheimer's Disease, a hallmark of which is decreased brain glucose metabolism. Dietary sources of aluminum include that which comes from the contact of food with aluminum cook ware, containers, foil, and utensils. Normal aluminum intake from all sources is estimated as 12-14 mg per day. We have evaluated brain glucose metabolism in the presence of physiologically achievable levels of aluminum, in the range 10(-15) to 10(-5) M. Our results indicate no effect of aluminum in the range tested. Thus the contact of food with aluminum cooking utensils cannot alone raise plasma aluminum concentrations to the millimolar levels required to decrease brain glucose metabolism. Non dietary pathophysiological mechanisms are operating which lead to the accumulation of tissue aluminum, since most of dietary aluminum is excreted by the kidney.
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PMID:Dietary aluminum and Alzheimer's disease. 129 88

A decrement in glucose utilization in brain was previously demonstrated in Alzheimer's disease (AD) and this abnormality has been proposed to play a role in the process of neuronal degeneration. We now report that glucose deprivation in cultured hippocampal neurons can result in antigenic alterations similar to those seen in AD neurofibrillary tangles (NFT) and, ultimately, cell death. Hypoglycemia caused an increase in neuronal immunoreactivity toward tau and ubiquitin antibodies. The antigenic alterations resulted from hypoglycemia-induced elevations in intracellular calcium levels as measured using the calcium indicator dye fura-2. The increased intraneuronal calcium levels, increased tau and ubiquitin immunoreactivities, and neuronal damage resulted from influx through the plasma membrane since they were not observed when cells were incubated in calcium-deficient medium. Neuronal damage and NFT-like antigenic changes were completely prevented by nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), but not by epidermal growth factor (EGF). NGF and bFGF, but not EGF, prevented the aberrant rise in intracellular calcium levels that normally resulted from glucose deprivation. These data are consistent with the possibility that reduced glucose availability to neurons may contribute to the neuronal degeneration that occurs in AD. They also suggest that growth factors may normally protect neurons against hypoglycemic damage.
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PMID:Glucose deprivation elicits neurofibrillary tangle-like antigenic changes in hippocampal neurons: prevention by NGF and bFGF. 132 83

Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a drug that has attained interest because of its ability to alleviate symptoms in Alzheimer's type of dementia, was found to stimulate insulin secretion from isolated rat pancreatic islets. The insulinotropic effect of the drug was observed at 8.3 mM but not at 3.3 mM glucose and was dependent on extracellular Ca++. From perifused 86Rb(+)-prelabeled islets, tacrine inhibited the fractional efflux of 86Rb+ at 3.3 mM glucose, but stimulated 86Rb+ efflux at 8.3 mM glucose. These effects persisted in the absence of extracellular Ca++. Tacrine also stimulated 45Ca++ efflux from perifused 45Ca(++)-prelabeled islets at 8.3 mM but had no effect on 45Ca++ efflux at 3.3 mM glucose or in the absence of extracellular Ca++. It is concluded that tacrine potentiates glucose-stimulated insulin secretion by a mechanism that is dependent on extracellular Ca++ and involves an increased Ca++ influx. The increased Ca++ influx is either secondary to a decreased K+ permeability induced by an inhibition of ATP-dependent K+ channels and/or due to a direct effect of tacrine on glucose-activated Ca++ channels.
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PMID:Effects of tacrine on insulin secretion and 86Rb+ and 45Ca++ efflux from rat pancreatic islets. 133

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.
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PMID:Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease. 140 Jun 46

Positron emission tomography (PET) is the only method that measures concomitantly in the same cerebral region the main haemodynamic (blood flow, blood volume) and metabolic (oxygen and glucose consumption) parameters, thereby providing essential data concerning the supply of substrates by circulation and their principally neuronal/synaptic use by the cells. In "healthy" (i.e. normal) ageing, there is a progressive decrease of oxygen and glucose consumption--with subsequent reduction of cerebral blood flow (CBF)--which predominates in the neocortex and suggests a dysfunction of neuronal circuits perhaps responsible for some age-related changes in cognitive functions. The metabolic depression in the neocortex seems to be accentuated during the more "common" ageing which may include cerebrovascular risk factors, lesions of the white matter in varying numbers and/or degradation of cognitive functions. Strategically located brain lesions of vascular origin (e.g. damaging of the thalamic nuclei), may produce a thalamo-cortical disconnection which induces a diffuse cortical hypometabolism associated with severe cognitive disorders. In degenerative dementias (particularly Alzheimer's disease), which include cortical and subcortical neuronal lesions (e.g. those involving the cholinergic system), there is a hypometabolism preferentially affecting the associative cortex. The cumulative effects on cortical functioning of multiple vascular lesions, superimposed on degenerative neuron loss, might account for age-related cognitive disorders in "normal" ageing as well as in the so-called "vascular" or "mixed" dementias.
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PMID:[Cerebral and cardiovascular aging and brain energy metabolism. Studies with positron-emission tomography in man]. 140 78

Reduction of the cerebral metabolic rate of glucose is one of the most predominant abnormalities generally found in the Alzheimer brain, whereas the cerebral metabolic rate of oxygen is only slightly diminished or not at all the beginning of this dementive disorder. This metabolic abnormality may induce severe functional disturbances, obviously preceding morphobiological changes. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral ATP formation rate was calculated in incipient early-onset, incipient late-onset and stable advanced dementia of Alzheimer type. A reduction of ATP formation was found from at least 7% in incipient early-onset, to around 20% in incipient late-onset DAT, and from 35% to more than 50% in stable advanced dementia. This approximation was adjusted to findings demonstrating diminished activities of enzymes active in glucose metabolism and formation of oxidation equivalents for ATP production from substrates other than glucose. A reduction for energy formation to the same range was found, as was also recently reported, in vivo in Alzheimer patients. From this rather theoretical point of view, a permanent loss of energy by at least 7-20% in incipient and progressively advancing dementia of the Alzheimer type may be assumed, with an increasing tendency in stable advanced dementia to around 50% energy loss. This energy deficit may have drastic impacts on brain function.
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PMID:Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late-onset cases. 141 18

In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.
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PMID:Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles. 143 60


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