Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233794 (memory impairment)
 7,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to memory impairment, deficits in other cognitive processes are common in the advanced stages of Alzheimer's disease (AD). The diagnosis of AD does not consider the relative prevalence of deficits in cognitive areas other than memory. We report on the prevalence of aphasia, apraxia, and other cognitive changes in individuals from a large representative sample of elderly Canadians. The proportion of these symptoms and the relevant neuropsychological test performance were compared in a group of 749 people over 65 years in age with AD and a control group of 563 people without cognitive impairment. Agnosia was less common in both groups than were deficits in complex visuomotor tasks, abstract thinking, aphasia, and constructional defects. The occurrence of all symptoms increased, and levels of performance on relevant neuropsychological tests decreased, with severity of Alzheimer disease. The tests did not, however, distinguish between possible and probable AD. Both these diagnostic groups showed similar levels of performance, which suggests that this distinction is not clinically meaningful.
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PMID:Beyond memory impairment: cognitive changes in Alzheimer's disease. 1458 47

Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). Deposition of the amyloid-beta peptide (Abeta) in brain, particularly its 42-amino acid isoform (Abeta42), has been shown to play a primary and crucial role in the pathogenesis of AD. In this study we have developed a recombinant adeno-associated virus (AAV) vaccine against AD. This vaccine could express CB-Abeta42 (cholera toxin B subunit and Abeta42 fusion protein) in vivo. A single administration of the AAV-CB-Abeta42 vaccine induced a prolonged, strong production of Abeta-specific serum IgG in transgenic mice that overexpressed the London mutant of amyloid precursor protein (APP/V717I), and resulted in improved ability of memory and cognition, decreased Abeta deposition in the brain, and a resultant decrease in plaque-associated astrocytosis. Our results extended the immunological approaches for the treatment and prevention of AD to an oral, intranasal, or intramuscular route that might be better tolerated in human patients than repetitive parental immunizations in the presence of adjuvant. AAV has attracted tremendous interest as a promising vector for gene delivery. Our results raised the possibility that AAV-CB-Abeta42 vector immunization may provide the basis of a novel and promising Alzheimer's disease vaccination program.
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PMID:A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and beta-amyloid plaques in a mouse model of Alzheimer's disease. 1467 54

We investigated the effect of long-term oral administration of ethanolic extract of Angelica gigas Nakai (Umbelliferae) (EAG) or decursinol, a coumarin isolated from A. gigas, on beta-amyloid peptide 1-42 (Abeta(1-42))-induced memory impairment in mice. Mice were allowed free access to drinking water (control) or water containing different concentrations of EAG. After 4 weeks, Abeta(1-42) (410 pmol) was administered via intracerebroventricular injection. Pretreatment of mice with EAG (0.1%) for 4 weeks significantly blocked the Abeta(1-42)-induced impairment in passive avoidance performance. Next, mice were fed with chow mixed with various doses of decursinol for 4 weeks before intracerebroventricular injection of Abeta(1-42) (410 pmol). Pretreatment of mice with decursinol (0.001%, 0.002%, and 0.004%) for 4 weeks significantly attenuated the Abeta(1-42)-induced impairment in passive avoidance performance. Decursinol (0.004%) also significantly blunted the Abeta(1-42)-induced decrease in alternation behavior (spatial working memory) in the Y-maze test without change in general locomotor activity. These findings suggest that EAG or decursinol may have preventive effect against memory impairment related with Abeta of Alzheimer's disease.
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PMID:Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. 1468 53

Clinical trials report that Ginkgo biloba extracts (e.g., EGb761) reduce cognitive symptoms in age-associated memory impairment and dementia, including Alzheimer disease (AD). However, the mechanisms behind their neuroprotective ability remain to be fully established. In this study, the effect of EGb761 on the amyloid precursor protein (APP) metabolism has been investigated by both in vitro and in vivo models. To this aim, alpha-secretase, the enzyme regulating the non-amyloidogenic processing of APP and the release of alphaAPPs, the alpha-secretase metabolite, were studied in superfusates of hippocampal slices after EGb761 incubation, and in hippocampi and cortices of EGb761-treated rats. PKC translocation state was evaluated as well. EGb761 increases alphaAPPs release through a PKC-independent manner. This effect is not accompanied by a modification of either APP forms or alpha-secretase expression. Moreover, EGb761 influence on alphaAPPs release was strictly dependent on treatment dosage. Our findings suggest that the benefit of EGb761 reported by previous clinical studies is underscored by a specific biological mechanism of this compound on APP metabolism, directly affecting the release of the non-amyloidogenic metabolite. Additional research will be needed to clearly define the effective clinical relevance, thus considering EGb761 as a possible supplementary treatment in dementing diseases.
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PMID:Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. 1519 1

In the present study we examined the long-term effects of neonatal lesion of basal forebrain cholinergic neurons induced by intracerebroventricular injections of the immunotoxin 192 IgG saporin. Animals were then characterised behaviourally, electrophysiologically and molecularly. Cognitive effects were evaluated in the social transmission of food preferences, a non-spatial associative memory task. Electrophysiological effects were assessed by recording of cortical electroencephalographic (EEG) patterns. In addition, we measured the levels of proteins whose abnormal expression has been associated with neurodegeneration such as amyloid precursor protein (APP), presenilin 1 and 2 (PS-1, PS-2), and cyclooxygenases (COX-1 and COX-2). In animals lesioned on postnatal day 7 and tested 6 months thereafter, memory impairment in the social transmission of food preferences was evident, as well as a significant reduction of choline acetyltransferase activity in hippocampus and neocortex. Furthermore, similar to what observed in Alzheimer-like dementia, EEG cortical patterns in lesioned rats presented changes in alpha, beta and delta activities. Levels of APP protein and mRNA were not affected by the treatment. Levels of hippocampal COX-2 protein and mRNA were significantly decreased whereas COX-1 remained unaltered. PS-1 and PS-2 transcripts were reduced in hippocampus and neocortex. These findings indicate that neonatal and permanent basal forebrain cholinergic hypofunction is sufficient to induce behavioural and neuropathological abnormalities. This animal model could represent a valid tool to evaluate the role played by abnormal cholinergic maturation in later vulnerability to neuropathological processes associated with cognitive decline and, possibly, to Alzheimer-like dementia.
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PMID:Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats. 1529 46

We have demonstrated that oxidative stress is involved, at least in part, in beta-amyloid protein (Abeta)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Abeta remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Abeta (1-42) in mice. Abeta (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Abeta (40-1)-treated mice. Treatment with antioxidant alpha-tocopherol significantly prevented memory impairment induced by Abeta (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Abeta (1-42)-treated animals, as compared with Abeta (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Abeta (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Abeta (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2h after Abeta (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Abeta (1-42), but the antioxidant alpha-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Abeta (1-42)-induced learning and memory deficits in mice.
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PMID:Beta-amyloid (1-42)-induced learning and memory deficits in mice: involvement of oxidative burdens in the hippocampus and cerebral cortex. 1536 77

We previously reported that (-)-nicotine and kappa-opioid receptor agonists lessened impairment of learning and/or memory in several animal models. Furthermore, these drugs prevented neurodegenerative damage induced by ischemia or beta-amyloid peptide (25-35). In the present study, we tested whether (-)-nicotine and U-50,488H prevent delayed-memory impairment induced by beta-amyloid peptide (25-35), and changes of expression of alpha7-type nicotinic acetylcholine receptor mRNA and prodynorphin mRNA. Seven days after treatment with beta-amyloid peptide (25-35) (9 nmol/mouse, i.c.v.), memory impairment was observed in the Y-maze test. Memory impairment was prevented when (-)-nicotine (6.16 micromol/kg, s.c.) or U-50,488H (21 micromol/kg, s.c.) was administered 1 h before, but not 1 h after, beta-amyloid peptide (25-35) treatment. There was no change in prodynorphin mRNA or alpha7-type nicotinic acetylcholine receptor mRNA expression in the hippocampus 10 days after beta-amyloid peptide (25-35) treatment alone. Of interest, mRNA expression of not only prodynorphin, but also the alpha7-type nicotinic acetylcholine receptor, was significantly decreased when U-50,488H was administered 1 h before, but not 1 h after, treatment with beta-amyloid peptide (25-35). However, these changes were not observed after the administration of (-)-nicotine. These results suggest that activation of the kappa-opioid system, but not beta7-type nicotinic receptors has a neuroprotective effect on beta-amyloid peptide (25-35)-induced memory impairment, and may be involved in the long-lasting changes in the expression of these mRNAs.
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PMID:Alpha 7-type nicotinic acetylcholine receptor and prodynorphin mRNA expression after administration of (-)-nicotine and U-50,488H in beta-amyloid peptide (25-35)-treated mice. 1554 56

Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.
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PMID:ApoE isoform affects LTP in human targeted replacement mice. 1557 Jan 72

The abnormal hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer disease and other tauopathies; as yet the exact role of various tau kinases in this pathology is not fully understood. Here, we show that injection of isoproterenol, an activator of cAMP-dependent kinase (PKA), into rat hippocampus bilaterally results in the activation of PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibition of protein phosphatase-2A, hyperphosphorylation of tau at several Alzheimer-like epitopes and a disturbance of spatial memory retention 48 h after the drug injection. These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment.
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PMID:Bilateral injection of isoproterenol into hippocampus induces Alzheimer-like hyperphosphorylation of tau and spatial memory deficit in rat. 1562 Jul 22

Progressive memory impairment, beta-amyloid (Abeta) plaques associated with local inflammation, neurofibrillary tangles, and loss of neurons in selective brain areas are hallmarks of Alzheimer's disease (AD). Although beta-amyloid precursor protein (APP) and Abeta have a central role in the etiology of AD, it is not clear which forms of APP or Abeta are responsible for the neuronal vulnerability in AD brain. Brain ischemia, another cause of dementia in the elderly, has recently been recognized to contribute to the pathogenesis of AD and individuals with severe cognitive decline and possibly underlying AD are at increased risk for ischemic events in the brain. Moreover, the epsilon4 allele of apolipoprotein E (ApoE) is a risk factor for both AD and poor outcome following brain ischemia and hemorrhage. Several factors and molecular mechanisms that lower the threshold of neuronal death in models of AD have recently been described. Among these neuroinflammation seems to play an important role. The development and maturation of both AD neuropathology and ischemic lesions in the central nervous system are characterized by activation of glial cells and upregulation of inflammatory mediators. Indeed, anti-inflammatory approaches have proven to be beneficial in the prevention and treatment of AD-like neuropathology and ischemic injuries in vivo. This review summarizes some of the findings suggesting that neuronal overexpression of human APP renders the brain more vulnerable to ischemic injury and describes the factors that are involved in increased neuronal susceptibility to ischemic stroke.
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PMID:Interactions between Alzheimer's disease and cerebral ischemia--focus on inflammation. 1585 Jun 63


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