Abstract:
:The amyloid beta-peptide (A beta)-associated free radical oxidative stress model for neuronal death in Alzheimer's disease (AD) brain predicts that neuronal protein oxidation is a consequence of A beta-associated free radicals [8]. In this study we have used both in vitro and in vivo models of beta-amyloid (A beta) toxicity to detect free radical induced oxidative stress by the measure of protein carbonyl levels. These model systems employed cultured hippocampal neurons exposed to exogenous synthetic A beta(1-42) and transgenic Caenorhabditis elegans (C. elegans) animals expressing A beta(1-42). We also investigated the importance of the A beta(1-42) Met35 residue for free radical formation in peptide solution and for peptide-induced protein oxidation and neuronal toxicity in these model systems. A beta(1-42) in solution yielded an EPR spectrum, suggesting that free radicals are associated with this peptide; however, neither the reverse [A beta(42-1)] nor methionine-substituted peptide [A beta(1-42)Met35Nlc] gave significant EPR spectra, suggesting the importance of the methionine residue in free radical formation. A beta(1-42) addition to cultured hippocampal neurons led to both neurotoxicity (30.1% cell death, p < 0.001) and increased protein oxidation (158% of controls, p < 0.001). and both of those effects were not observed with reverse or Met35Nle substituted peptides. C. elegans transgenic animals expressing human A beta(1-42) also had significantly increased in vivo protein carbonyls (176% of control animals, p < 0.001), consistent with our model. In contrast, transgenic animals with a Met35cys substitution in A beta(1-42) showed no increased protein carbonyls in vivo, in support of the hypothesis that methionine is important in A beta-associated free radical oxidative stress. These results are discussed with reference to the A beta-associated free radical oxidative stress model of neurotoxicity in AD brain.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Yatin SM,Varadarajan S,Link CD,Butterfield DAdoi
10.1016/s0197-4580(99)00056-1subject
Has Abstractpub_date
1999-05-01 00:00:00pages
325-30; discussion 339-42issue
3eissn
0197-4580issn
1558-1497pii
S0197458099000561journal_volume
20pub_type
杂志文章abstract::To better understand the role of insulin signaling in the development of Alzheimer's disease (AD), we utilized an animal model (intracerebroventricular injection of streptozotocin-ic-streptozotocin (STZ)) that displays insulin resistance only in the brain and exhibits AD pathology. In this model, deficits in hippocamp...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2010.12.002
更新日期:2012-02-01 00:00:00
abstract::The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.07.018
更新日期:2014-01-01 00:00:00
abstract::Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,meta分析
doi:10.1016/j.neurobiolaging.2019.08.020
更新日期:2020-02-01 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::Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Si...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.08.015
更新日期:2016-12-01 00:00:00
abstract::The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.09.019
更新日期:2008-02-01 00:00:00
abstract::We have measured several morphological parameters by electron microscopy of the frontal cortex (FC) and hippocampal CA1 (HC) capillaries in male Fischer 344 rats 3-, 9- and 24-months old. The results indicate that with increasing age there is an increase in the cross-sectional area of the basement membrane, increase i...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(83)90057-x
更新日期:1983-04-01 00:00:00
abstract::Deficits in synaptic structure and function are likely to underlie cognitive impairments in Alzheimer's disease. While synaptic deficits are commonly found in animal models of amyloidosis, it is unclear how amyloid pathology may impair synaptic functions. In some amyloid mouse models of Alzheimer's disease, however, s...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.07.009
更新日期:2016-11-01 00:00:00
abstract::The associations of 4 proteins-AK4, ITPK1, HSPB2, and IGFBP5-with cognitive function in older adults were largely unexplained by known brain pathologies. We examined the extent to which individual protein associations with cognitive decline were attributable to microstructural changes in the brain. This study included...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.07.013
更新日期:2019-12-01 00:00:00
abstract::Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPα) having neuroprotective properties and the beta amyloid (Aβ) peptide at the origin of neurotoxic oligomers, particularly Aβ1-42. Whether extracellular Aβ1-42 oligomers m...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.09.008
更新日期:2018-01-01 00:00:00
abstract::Aged, cognitively-impaired rats (and humans) show hypothalamic-pituitary-adrenal (HPA) hyperactivity that correlates with hippocampal damage. The resultant increase in plasma glucocorticoid exposure is thought to contribute to impaired hippocampal function and to potentiate hippocampal neuron death. In young, adult ra...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(97)00103-6
更新日期:1997-09-01 00:00:00
abstract::In this study, the Purkinje neurons and granule neurons in the cerebellar cortex were studied in male Fischer 344 rats at 3, 9, 18, and 27 months of age. The numbers of Purkinje cells (PC) and granule cells (GC) in folia IV, VII, and X of the vermis were quantitated with the disector stereological technique. The numbe...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(94)90075-2
更新日期:1994-07-01 00:00:00
abstract::Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated w...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2011.06.012
更新日期:2012-09-01 00:00:00
abstract::Here we report the relationship between age at onset, clinical course and genotype in a family with combined LRRK2 G2019S and Parkin exon 2 deletions. In the combined mutation carriers the age at onset and clinical course was highly variable and not always younger than in the carriers of LRRK2 G2019S mutations alone. ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2008.05.030
更新日期:2010-04-01 00:00:00
abstract::We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose signifi...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(94)90141-4
更新日期:1994-01-01 00:00:00
abstract::The increased life expectancy of people living with HIV-1/AIDS is accompanied by increased prevalence of HIV-1-associated neurocognitive disorder. As well, these individuals are increasingly experiencing Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased deposition o...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.04.015
更新日期:2013-10-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In t...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.01.016
更新日期:2017-05-01 00:00:00
abstract::Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2011.02.006
更新日期:2011-06-01 00:00:00
abstract::Vascular risk factors have been implicated in the pathogenesis of vascular dementia and Alzheimer's disease. The identification of a novel vascular disease susceptibility locus at 9p21.3 has recently generated great interest. In the present study, we sought to determine whether a common genetic variant (tagged by rs13...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2009.07.003
更新日期:2011-07-01 00:00:00
abstract::Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In thi...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.06.019
更新日期:2020-11-01 00:00:00
abstract::We recently reported evidence for an association between the individual variation in normal human episodic memory and a common variant of the KIBRA gene, KIBRA rs17070145 (T-allele). Since memory impairment is a cardinal clinical feature of Alzheimer's disease (AD), we investigated the possibility of an association be...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2008.07.014
更新日期:2010-06-01 00:00:00
abstract::To investigate whether dramatically waned dentate neurogenesis during aging is linked to diminution in neural stem/progenitor cell (NSC) number, we counted cells immunopositive for Sox-2 (a putative marker of NSCs) in the subgranular zone (SGZ) of young, middle-aged and aged F344 rats. The young SGZ comprised approxim...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.09.015
更新日期:2008-01-01 00:00:00
abstract::Delivery of drugs to specific sites in the CNS represents an essential therapeutic challenge. Extradural administration of opiates successfully delivers drugs to the CNS. The levodopa-carbidopa combination achieved some degree of site-specific delivery by pharmacological methods. Antibiotics have been administered thr...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(89)90156-5
更新日期:1989-09-01 00:00:00
abstract::The objective of this study was to examine the distribution and severity of tau-PET binding in cognitively normal adults with preclinical Alzheimer's disease as determined by positive beta-amyloid PET. 18F-AV-1451 tau-PET data from 109 cognitively normal older adults were processed with 34 cortical and 9 subcortical F...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.08.022
更新日期:2018-12-01 00:00:00
abstract::Sporadic Alzheimer's disease (AD) appears to be the consequence of the interaction between combinations of genes and environmental factors. Binding with the transporter associated with antigen processing (TAP) is thought to be the main way in which herpes simplex virus type 1 (HSV-1) evades immune surveillance. Severa...
journal_title:Neurobiology of aging
pub_type: 杂志文章,多中心研究
doi:10.1016/j.neurobiolaging.2006.02.011
更新日期:2007-04-01 00:00:00
abstract::White matter is frequently involved in ischemic stroke, and progressive ischemic white matter injuries are associated with various neurologic dysfunctions in the elderly population. Demyelination and oligodendrocyte (OL) loss are prominent features of ischemic white matter injury. Endothelin-1 injection into the inter...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.01.146
更新日期:2014-07-01 00:00:00
abstract::In the present study, we aim at investigating whether education modulates dynamical properties of time-varying whole-brain network connectivity (the chronnectome) in frontotemporal dementia (FTD) at a given level of symptom severity. Dynamic connectivity parameters were evaluated in 128 patients with FTD using indepen...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.04.021
更新日期:2020-09-01 00:00:00
abstract::Variants associated with modulation of c-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease risk variants. We examined pleiotropic genetic effects on cognitive impairment conditioned on genetic variants (SNPs) associated with systemic inflammation as measured...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.10.028
更新日期:2019-08-01 00:00:00
abstract::Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (Neur...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.07.038
更新日期:2015-01-01 00:00:00
abstract::Although it was suggested that gangliosides play an important role in the binding of amyloid fragments to neuronal cells, the exact role of gangliosides in Alzheimer's disease (AD) pathology remains unclear. To understand the role of gangliosides in AD pathology in vivo, we crossed st3gal5-deficient (ST3-/-) mice that...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.01.020
更新日期:2019-05-01 00:00:00