Abstract：
:The application of beta-amyloid (Abeta) is cytotoxic to endothelial cells, promotes vasoconstriction and impairs nitric oxide (NO) generation or action. However, there is no information on the effect of intracellular Abeta on endothelial cell biology, although recent studies indicate that neuronal Abeta drives Alzheimer's disease pathogenesis. Since the serine-threonine kinase Akt is crucial to both neuronal and endothelial cell survival as well as eNOS activation, we investigated the effects of Abeta expression on Akt-signaling in cultured endothelial cells. Virally-encoded Abeta42 was proapoptotic and inhibitory to Akt phosphorylation in human umbilical vein endothelial cells (HUVECs). Toxicity was characterized by mitochondrial dysfunction, DNA condensation and activation of caspase-3. Substrates downstream of Akt action, GSK-3beta and eNOS, are underphosphorylated in the presence of Abeta. Constitutive activation of Akt reversed Abeta-induced toxicity and stimulated caspase-3 activity, suggesting that inhibition of Akt signaling is functionally significant. These Abeta effects were mediated, in part, through the derepression of GSK-3beta activation and correlated with reductions in NO production. We conclude that intracellular production of Abeta42 is cytotoxic to endothelial cells and that disruption of the Akt/GSK-3beta cell signaling pathway is involved.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Suhara T,Magrané J,Rosen K,Christensen R,Kim HS,Zheng B,McPhie DL,Walsh K,Querfurth Hdoi
10.1016/s0197-4580(02)00135-5subject
Has Abstractpub_date
2003-05-01 00:00:00pages
437-51issue
3eissn
0197-4580issn
1558-1497pii
S0197458002001355journal_volume
24pub_type
杂志文章abstract：:The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, an...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.021
更新日期：2006-05-01 00:00:00
abstract：:Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.12.009
更新日期：2014-06-01 00:00:00
abstract：:Alzheimer's disease (AD) is generally considered to be a disorder primarily affecting memory. It is increasingly recognized that the clinical presentation or "cognitive phenotype" is variable. The apolipoprotein E ε4 (APOE ε4) allele has been associated with an amnestic presentation, but does not appear to fully expla...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.11.003
更新日期：2012-07-01 00:00:00
abstract：:Counts of neurons in locus coeruleus of Fisher 344 rats of ages from 12 to 32 months showed no loss with advancing age. Species comparisons of age changes in locus coeruleus neuron counts and measures of catecholamine systems suggested that the human and nonhuman primate locus coeruleus shows age changes and seen in r...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(81)90056-7
更新日期：1981-04-01 00:00:00
abstract：:Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.12.027
更新日期：2013-07-01 00:00:00
abstract：:A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.03.017
更新日期：2020-08-01 00:00:00
abstract：:Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and su...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.08.005
更新日期：2014-02-01 00:00:00
abstract：:There is a marked increase with advancing age of stimulation-evoked neurotransmitter release from vascular adrenergic nerves in the rat, an effect correlated with increased levels of plasma norepinephrine. This increase in norepinephrine release could not be accounted for by an alteration in neuronal and extraneuronal...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(96)00179-0
更新日期：1996-11-01 00:00:00
abstract：:Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they associate with cholesterol concentrations and, for rs6084, coronary artery disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent e...
journal_title：Neurobiology of aging
pub_type： 杂志文章,多中心研究
doi：10.1016/j.neurobiolaging.2006.11.015
更新日期：2008-05-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.011
更新日期：2015-03-01 00:00:00
abstract：:Neuronal alphabeta heteromeric and alpha7 homomeric nicotinic acetylcholine receptors (nAChRs) were compared in 4- and 27-month rabbits selected for learning proficiency. Sixty 4- and 60 27-month rabbits received the alpha7 nAChR agonist (MEM-3389), galantamine, or vehicle during training in trace eyeblink classical c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.09.002
更新日期：2010-06-01 00:00:00
abstract：:The three chapters on the use of classical conditioning paradigms to investigate neurobiological and behavioral substrates of memory impairments with aging are in close agreement on all key issues. Based on these chapters, it is argued here that classical conditioning of discrete behavioral responses in rabbit and oth...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(88)80111-8
更新日期：1988-09-01 00:00:00
abstract：:Recent studies have implicated increased oxidative stress in the pathogenesis of Alzheimer's disease (AD). Increased lipid peroxidation and decreased polyunsaturated fatty acid levels have been described in the brain in AD. Four-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been demonstrated to ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00009-8
更新日期：1998-01-01 00:00:00
abstract：:We recently reported that mutations in the valosin-containing protein (VCP) gene are a cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases, but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of VCP in 701 sporadic ALS cases. Three pathogenic variants (p.Ar...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.04.005
更新日期：2012-09-01 00:00:00
abstract：:The activities of presenilin 1 (PS1) and 2 modulate the proteolytic processing of amyloid precursor proteins to produce Abeta1-42, and mutations in these proteins are associated with an accelerated rate of Abeta deposition. PS1 and PS2 themselves are subject to a highly-regulated endoproteolytic cleavage to generate s...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00280-9
更新日期：2002-03-01 00:00:00
abstract：:Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)00062-0
更新日期：1996-07-01 00:00:00
abstract：:The relationship between the neurofibrillary tangles and the intellectual deficit observed in senile dementia of the Alzheimer type was studied in 27 patients over the age of 75. The presence and density of tau positive tangles were assessed in six areas including limbic, paralimbic, and isocortical cortices. In the i...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)80306-5
更新日期：1997-05-01 00:00:00
abstract：:Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overal...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.001
更新日期：2016-04-01 00:00:00
abstract：:Deletions of the mitochondrial DNA (mtDNA) have been shown to accumulate with age in a variety of species regardless of mean or maximal life span. This implies that such mutations are either a molecular biomarker of senescence or that they are more causally linked to senescence itself. One assay that can be used to de...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(99)00092-5
更新日期：1999-09-01 00:00:00
abstract：:We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early-stage Alzheimer's disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy, and dementia progression. Individuals with early-stage AD (n = 37) and without dementia (...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.03.016
更新日期：2012-08-01 00:00:00
abstract：:This paper reports a series of experiments that assessed learning and memory performance in aged rats from a neuropsychological perspective. Relative to young adults, old rats displayed rapid rates of forgetting, increased susceptibility to interference, and poor long-term recall of specific experiences. There were no...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(88)80102-7
更新日期：1988-09-01 00:00:00
abstract：:Cortico-striatal-thalamic network functional connectivity (FC) and its relationship with levodopa (L-dopa) were investigated in 69 patients with hemiparkinsonism (25 drug-naïve [n-PD] and 44 under stable/optimized dopaminergic treatment [t-PD]) and 27 controls. Relative to controls, n-PD patients showed an increased F...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.05.032
更新日期：2014-11-01 00:00:00
abstract：:The growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine HCl (Apo) (0.5 mg SC) was studied in young and elderly normal subjects as well as in patients with dementia of the Alzheimer type (DAT) and controls matched for age, gender and Quetelet index. The GH response was significantly decrease...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(89)90055-9
更新日期：1989-05-01 00:00:00
abstract：:Demonstrations that grip strength has predictive power in relation to a range of health conditions-even when these are assessed decades later-has motivated claims that hand-grip dynamometry has the potential to serve as a "vital sign" for middle-aged and older adults. Central to this belief has been the assumption tha...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2018.07.023
更新日期：2018-11-01 00:00:00
abstract：:It is widely known that the tau protein that forms the aggregates found in tauopathies like Alzheimer's disease (AD) is hyperphosphorylated. Many of the sites that are hyperphosphorylated in AD can also be found phosphorylated in non-pathological control brains, although to a lesser extend. Among the different kinases...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.04.002
更新日期：2003-12-01 00:00:00
abstract：:We determined whether oxidative stress is an early event in the pathogenesis of sporadic Alzheimer disease (AD), and correlated oxidative stress with neuropsychological functions and neurofibrillary pathology in AD and mild cognitive impairment (MCI). Oxidative stress was measured as the percentage of astrocytes expre...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.01.016
更新日期：2006-02-01 00:00:00
abstract：:Chronic circadian disturbance, a condition of desynchronization between endogenous clock and environmental light-dark (LD) cycle, is known to cause adverse physiological changes including mortality. However, it is yet unclear whether these consequences result from disturbance of endogenous clock or condition of the LD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.005
更新日期：2012-06-01 00:00:00
abstract：:Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), ofte...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.09.012
更新日期：2012-05-01 00:00:00
abstract：:Association of the A2 allele of the human leukocyte antigen (HLA) with Alzheimer disease (AD) is still controversial. The authors evaluated HLA-A2 association with AD in 173 Italian AD patients, considering also the possible interaction with APOE pattern, age of onset and gender. No evidence of any association was fou...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.02.001
更新日期：2009-12-01 00:00:00
abstract：:Aging is accompanied by declines in memory performance, and particularly affects memories that rely on hippocampal-cortical systems, such as episodic and explicit. With aged populations significantly increasing, the need for preventing or rescuing memory deficits is pressing. However, effective treatments are lacking....
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.04.006
更新日期：2016-08-01 00:00:00
