Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751295 (memory loss)
 3,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 59-year-old demented Japanese man who was proven to have high titer of serum alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) was admitted to our hospital. Neurological examinations revealed moderate dementia with deterioration and loss of memory, and decreased deep tendon reflexes in all extremities. Sensory disturbances were not obvious. There were no significant changes in the usual laboratory findings including CSF, except for elevated serum AFP and CEA. Three months after admission, he died of gastric cancer and its metastases in liver and lymph nodes. Post-mortem examination in the central nervous system (CNS) revealed many senile plaques and neurofibrillary tangles throughout the cerebral cortex and hippocampus. There was marked loss of neurons in the hippocampus. All the neuropathological findings in the CNS were consistent with those in Alzheimer disease. In the peripheral nervous system, necrotizing arteritis was found throughout the length of sciatic nerve. Large myelinated fibers seemed to be preferentially degenerated with proximo-distal gradient. Teased fiber preparation revealed de/remyelination and axonal degeneration more frequently at the distal portion. Immunohistologically, the serum IgG of this patient specifically reacted to the endothelial cells of all vessels in control organs, which strongly suggested the autoimmune mechanism for the necrotizing arteritis in this patient. The pathogenetic role of this antibody for necrotizing arteritis, found selectively in the peripheral nervous system, still remained unclear. However, paraneoplastic neuropathy due to necrotizing arteritis is a distinct entity in addition to common form of paraneoplastic subacute sensory neuropathy.
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PMID:[A case of paraneoplastic neuropathy with necrotizing arteritis localized in the peripheral nervous system]. 165 26

The discovery of a specific association between nerve growth factor (NGF) and basal forebrain cholinergic neurons (BFCNs) marks the beginning of a new era of research into neurodegenerative diseases such as Alzheimer disease (AD). Degeneration of BFCNs appears to be one of the earliest and most prominent neuropathological features of a broad range of diseases of the human brain that give rise to loss of memory and dementia (including, in addition to Alzheimer disease, Parkinson disease, Lewy body dementia, progressive supranuclear palsy, dementia pugilistica, olivopontocerebellar atrophy, and Wernicke-Korsakoff syndrome). Selective localization of NGF receptors on BFCN, the relatively high levels of NGF mRNA in BFCN target areas, and numerous effects of exogenous NGF in vivo and in vitro provide overwhelming evidence that the structure and function of BFCNs in the adult brain are dependent on this molecule. The question then arises as to how this special relationship is disturbed in the diseased human brain? Initial investigations in AD have already indicated a normality of NGF mRNA and retention of receptors in the basal forebrain region. Interpretation of these results and the therapeutic relevance of NGF obviously depend upon future developments in understanding the role of NGF in the normal and pathological brain.
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PMID:Nerve growth factor and the basal forebrain cholinergic system: a link in the etiopathology of neurodegenerative dementias? 218 Apr 39

The nature and severity of behavioral problems, and their relationship to cognitive and functional abilities, was investigated in 56 community-residing patients with Alzheimer's disease. Measures evaluated three domains of function: behavior, cognition and activities of daily living. Problems of cognitive functioning, such as memory loss, confusion, and disorientation were most prevalent, reported to occur in 84%, 82%, and 64% of the sample, respectively. Problems with activity and emotional distress were next, affecting 20 to 43% of the sample. The mean number of problems reported was 10 per patient. Twenty-two percent of caregivers reported a minimum of 15 problems occurring at least twice a week and no caregiver reported an absence of problems. Male patients were reported to have more behavioral difficulties. Level of behavioral disturbance was largely unrelated to cognitive or functional ability. Age was unrelated to cognitive or behavioral disturbance but significantly related to activities of daily living. Results indicated that behavioral problems are prevalent and pervasive in even moderately impaired community-residing Alzheimer disease patients, and that age may be more important than level of cognitive dysfunction in predicting difficulties with activities of daily living.
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PMID:Behavioral disturbance, cognitive dysfunction, and functional skill. Prevalence and relationship in Alzheimer's disease. 278 33

This article, basing on experimental analysis and clinical observations, focuses on the role of subcortical structures in memory processes. It explained terminological problems and defined terms of memory: immediate, delayed, recent, remote, declarative and procedural. The present article pointed out functional hemispheric specialization as a predicator of material-specific forms of memory. Neuroanatomical basis was revealed, especially limbic system with its connections to prefrontal, cortical and brain stem regions. Amnesic Korsakoff and Wernicke syndromes, transient global amnesia, memory loss after bilateral damage of temporal lobes and after anterior communicating artery aneurysm rupture, were also discussed. Next part exhibited current knowledge about definition of dementia which may be caused by many multi-focal brain diseases like multiinfarct (vascular) dementia, Parkinson disease, Huntington disease, and sclerosis multiplex, and compared to Alzheimer disease. Term of dementia was defined, according to Cummings and Benson, as syndrome of acquired intellectual dysfunction when three of the following mental functions are impaired: language, memory, visuospatial skills, emotion, and cognition (abstraction, calculation, judgement). There is little doubt that various subcortical diseases are characterised by similar, no specific dysfunctions of cognitive processes including: disturbed attention and concentration, slowness of mental processing, forgetfulness, personality alterations and mood disturbances as well as motivational impairment, visuospatial disturbances, absence of symptoms of cortical dysfunction such as aphasia, agnosia and apraxia and associated motor disorder. Review of the literature suggests that rapid forgetting and retrieval deficits are most often symptoms of memory deficits observed after subcortical brain injuries.
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PMID:[Neuropsychological description of memory impairment following cortical and subcortical brain injuries]. 756 22

Thiamine deficiency (TD) is a classical model of impaired cerebral oxidation. As in Alzheimer's disease (AD), TD is characterized by selective neuronal loss, decreased activities of thiamine pyrophosphate-dependent enzymes, cholinergic deficits and memory loss. Amyloid beta-protein (A beta), a approximately 4 kDa fragment of the beta-amyloid precursor protein (APP), accumulates in the brains of patients with AD or Down's syndrome. In the current study, we examined APP and A beta immunoreactivity in the brains of thiamine-deficient rats. Animals received thiamine-deficient diet ad libitum and daily injections of the thiamine antagonist, pyrithiamine. Immunocytochemical staining and immunoblotting utilized a rabbit polyclonal antiserum against human APP645-694 (numbering according to APP695 isoform). Three, 6 and 9 days of TD did not appear to damage any brain region nor change APP-like immunoreactivity. However, 13 days of TD led to pathological lesions mainly in the thalamus, mammillary body, inferior colliculus and some periventricular areas. While immunocytochemistry and thioflavine S histochemistry failed to show fibrillar beta-amyloid, APP-like immunoreactivity accumulated in aggregates of swollen, abnormal neurites and perikarya along the periphery of the infarct-like lesion in the thalamus and medial geniculate nucleus. Immunoblotting of the thalamic region around the lesion revealed increased APP-like holoprotein immunoreactivity. APP-like immunoreactive neurites were scattered in the mammillary body and medial vestibular nuclei where the lesion did not resemble infarcts. In the inferior colliculus, increased perikaryal APP-like immunostaining occurred in neurons surrounding necrotic areas. Regions without apparent pathological lesions showed no alteration in APP-like immunoreactivity. Thus, the oxidative insult associated with cell loss, hemorrhage and infarct-like lesions during TD leads to altered APP metabolism. This is the first report to show a relationship between changes in APP expression, oxidative metabolism and selective cell damage caused by nutritional/cofactor deficiency. This model appears useful in defining the role of APP in the reponse to central nervous system injury, and may also be relevant to the pathophysiology of Wernicke-Korsakoff syndrome and AD.
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PMID:Accumulation of amyloid precursor protein-like immunoreactivity in rat brain in response to thiamine deficiency. 760 69

The identification of mutations in the amyloid precursor protein (APP) gene associated with the presence of early-onset familial Alzheimer disease (AD) raises the possibility of their practical clinical application, at least in some circumstances, in the diagnostic assessment for AD. As a stimulus for discussion, a hypothetical, illustrative case vignette is presented. A 48-year-old man, concerned about recent memory loss and with a family history of early-onset AD, requested testing for the APP717 Val-->Ile mutation, previously identified in his relatives affected with AD. Whether the testing should be undertaken is considered in the context of the current interpretation of potential test results as well as the competency of the individual who requested the test to provide informed consent. Informed consent includes an understanding of the foreseeable risks and benefits associated with disclosure of test results. Although molecular genetic testing in particular individuals, such as the man described herein, could be appropriate, it should not be interpreted to apply in general at this stage to individuals suspected of having AD. In view of a number of caveats, including the genetic heterogeneity of AD, which significantly limits the sensitivity and specificity of the currently available genetic tests, further research and discussion is strongly recommended before widespread introduction of molecular genetic testing for individuals with suspected AD.
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PMID:Issues in molecular genetic testing of individuals with suspected early-onset familial Alzheimer's disease. 806 Jun 4

Alzheimer's disease is a degenerative disorder of the human central nervous system that results in a progressive loss of memory and intellectual abilities. It is strongly related to aging and it is thus assumed that 0.5% of the total population, and up to 30% of eighty-year-olds suffer from the disease. Many require expensive institutional care, often over long periods, as there is no effective treatment at present. Abundant amyloid plaques and neurofibrillary tangles constitute the two major neuropathological lesions that characterize the brains of patients with Alzheimer's disease. The amyloid plaque consists mainly of a soluble polypeptide of 42-43 amino acids called beta-amyloid. beta-Amyloids is derived by an alternative cleavage of the much larger amyloid precursor protein (APP), but it is not known which proteolytic enzyme is responsible for this alternative cleavage. In contrast to plaques, the neurofibrillary tangles are formed intracellularly and the number of them seems to correlate with the progression of the disease. Their main components are paired helical filaments (PHF) which seem to consist almost entirely of the protein tau. The normal function of tau is to bind to microtubules and thereby stabilize the nerve cell's structure and integrity. In contrast to normal tau, PHF-tau is heavily phosphorylated, and it is assumed that this phosphorylation is the underlying cause of the formation of PHF and the neurofibrillary tangles. Despite extensive research it is still not known which enzymes are responsible for the over phosphorylation of tau that occurs in Alzheimer's disease. If they could be identified and controlled pharmacologically, an effective treatment of the disease might be possible.
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PMID:[Tau, amyloid and Alzheimer's disease]. 811 89

Alzheimer's disease (AD) is characterized pathologically by two distinguishable deposits in the brain, namely senile plaques and neurofibrillary tangles (NFT). Senile plaques are composed of fragments of the amyloid precursor protein, whereas NFT are composed primarily of paired-helical filaments (PHF). The latter are in turn composed principally of the microtubule-associated protein, tau. Tau in PHF is highly and unusually phosphorylated but the mechanisms leading to this unusual phosphorylation are not known. Using a combination of immunoblotting and kinase assays, we demonstrate that a discreet set of kinases copurify with PHF. One of these kinases was found by immunoblotting to be alpha-calcium-calmodulin-dependent kinase II (alpha-CaM kinase). Immunogold labeling revealed that alpha-CaM kinase was localized to a novel globular membranelike structure found at the ends of PHF. Since previous studies have shown alpha-CaM kinase to be involved in memory, its association with PHF may have important implications in understanding memory loss in AD. We also discuss the possibility that the association of alpha-CaM kinase with PHF may indicate sites where tau protein is converted into PHF.
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PMID:alpha-calcium-calmodulin-dependent kinase II is associated with paired helical filaments of Alzheimer's disease. 880 91

Patients with Alzheimer's disease (AD) show loss of memory and cognitive deficits the molecular mechanisms of which are not completely known. We examined age-related changes in the expression levels of beta-amyloid precursor protein (beta APP) in the brain of the senescence accelerated mouse (SAM) P/10, which shows age-dependent brain atrophy and impairment in learning and memory, and in the senescence resistant mouse (SAM)-R/1 using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Levels of both beta APP mRNA and protein increased with age, reaching a peak at 8 months of age in the hippocampus of SAM-P/10. In contrast, beta APP protein level decreased with age in the hippocampus of SAM-R/1 while beta APP mRNA level did not change significantly. Levels of beta APP mRNA and protein showed no change with ageing in other brain regions, including cerebral cortex, thalamus/midbrain and cerebellum brain stem. These results suggest that the beta APP over-expression in the hippocampus might be related to the characteristic memory loss in SAM-P/10.
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PMID:Age-related changes in the expression of Alzheimer's beta APP in the brain of senescence accelerated mouse (SAM)-P/10. 918 23

Both the early and late-onset Alzheimer's disease affect millions of people throughout the world. A number of molecules have been implicated in the pathogenesis of Alzheimer's disease. These include presenilin 1 and 2 (PS1 and PS2), a beta-amyloid peptide, and tau protein. Presenilin 1 and 2 genes implicated in the early-onset familial Alzheimer's disease have been cloned. Both PS1 and PS2 are integral membrane proteins and may function as receptors or channel proteins. Missense mutations in PS1 and PS2 genes have been found in families that cosegregate with early-onset Alzheimer's disease. Overexpression of the mutated PS1 gene produced amyloid plaques in the brain of transgenic mice. Secreted beta-amyloid protein similar to that in the senile plaques of Alzheimer's disease was found to be elevated in fibroblast media from subjects with PS1 or PS2 mutations. Transgenic mice which carried the mutant form of the beta-amyloid precursor protein gene expressed high concentrations of mutant copy of the gene and exhibited abundant amyloid plaques in the brain and memory loss. The mutated PS2 gene enhanced apoptotic activity. This enhanced apoptotic activity may accelerate the process of neurodegeneration leading to an earlier age in the onset of the disease. Identification of lesions in the molecules that are important in the Alzheimer's disease should allow developing therapeutic approaches for its treatment.
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PMID:Genes implicated in the pathogenesis of Alzheimer's disease. 920 74


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