Abstract:
:Studies in vitro have suggested that acetylcholinesterase (AChE) may interact with beta-amyloid to promote deposition of amyloid plaques in the brain of patients with Alzheimer's disease. To test that hypothesis in vivo, we crossed Tg2576 mice, which express human amyloid precursor protein and develop plaques at 9 months, with transgenic mice expressing human AChE. The resulting F1 hybrids (FVB/N x [C57B6 x SJL/J]) expressed both transgenes in brain. By 6 months of age, their cerebral cortex showed authentic plaques that stained both by thioflavin S and by beta-amyloid 1-40 and 1-42 immunohistochemistry. The plaques also stained positively for other components including Cd11b, GFAP, and AChE. Plaque onset in the hybrids occurred 30-50% sooner than in the parental lines. Plaque numbers increased with age and plaques remained more numerous in the doubly transgenic animals at 9 and 12 months. Quantitative immunoassay via ELISA also showed an increase of total amyloid content in brain at 9-12 months. These histological and biochemical results support the conclusion that AChE may play a role in pathogenesis of Alzheimer's disease
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Rees T,Hammond PI,Soreq H,Younkin S,Brimijoin Sdoi
10.1016/s0197-4580(02)00230-0subject
Has Abstractpub_date
2003-10-01 00:00:00pages
777-87issue
6eissn
0197-4580issn
1558-1497pii
S0197458002002300journal_volume
24pub_type
杂志文章abstract::Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therap...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2011.11.016
更新日期:2012-06-01 00:00:00
abstract::To characterize the mechanisms underlying region- and age-dependent hippocampal synaptic dysfunction in Alzheimer's disease, we used transgenic CRND8 mice, expressing the Swedish-Indiana APP mutation. In 2-month-old mice, no β-amyloid plaques deposition, but the presence of soluble oligomers, were found in CA1 area bu...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.07.002
更新日期:2015-01-01 00:00:00
abstract::In this study we employed an ELISA assay to measure alpha-synuclein protein in lymphomonocytes from 78 PD patients and 78 controls. We correlated protein levels with demographic and clinical characteristics and with the chymotryptic and tryptic activities of the 20S proteasome. Alpha-synuclein levels were not signific...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2008.06.010
更新日期:2010-05-01 00:00:00
abstract::In Parkinson disease, wild-type alpha-synuclein accumulates during aging, whereas alpha-synuclein mutations lead to an early onset and accelerated course of the disease. The generation of new neurons is decreased in regions of neurogenesis in adult mice overexpressing wild-type human alpha-synuclein. We examined the s...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.12.016
更新日期:2008-06-01 00:00:00
abstract::SORL1 encodes a 250-kDa protein named sorLA, a functional sorting receptor for the amyloid precursor protein (APP). Several single nucleotide polymorphisms of the gene SORL1, encoding sorLA, are genetically associated with Alzheimer's disease (AD). In the existing literature, SORL1 is insufficiently described at the t...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.06.021
更新日期:2018-11-01 00:00:00
abstract::Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments wi...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.12.011
更新日期:2013-06-01 00:00:00
abstract::In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.08.008
更新日期:2015-01-01 00:00:00
abstract::Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing fu...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.02.009
更新日期:2013-08-01 00:00:00
abstract::The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gr...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2008.04.007
更新日期:2010-03-01 00:00:00
abstract::Aging produces a loss in a number of behavioral and cognitive functions, including sleep. Hypocaloric diet is one of the few methods that have been shown to retard the effects due to age. However, the effects of such a diet on sleep have never been investigated. In the present study, 21 months old male F344 rats fed a...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00030-1
更新日期:2002-09-01 00:00:00
abstract::Amyloid deposits are one of the hallmarks of Alzheimer's disease. Recent studies, in transgenic mice modeling Alzheimer's disease showed that, using in vivo, contrast agent-free, MRI, thalamic amyloid plaques are more easily detected than other plaques of the brain. Our study evaluated the characteristics of these tha...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2007.05.018
更新日期:2009-01-01 00:00:00
abstract::Despite recognition that Alzheimer's disease (AD) is a polygenic and heterogeneous dementing neurodegenerative disorder, there is continued merit in defining the AD phenotype by the presence of progressive cognitive impairments and the pathological brain lesions (senile plaques, neurofibrillary tangles) as originally ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,评审
doi:10.1016/s0197-4580(97)00075-4
更新日期:1997-07-01 00:00:00
abstract::Fractal dimensionality (FD) measures the complexity within the folds and ridges of cortical and subcortical structures. We tested the degree that FD might provide a new perspective on the atrophy-compensation hypothesis: age or disease-related atrophy causes a compensatory neural response in the form of increased brai...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.10.023
更新日期:2020-11-14 00:00:00
abstract::Decreases in the activity or density of dopamine D2 receptor (D2R) have been associated with age-related changes and neurodegenerative diseases such as Parkinson's disease. There are two isoforms of the D2R, termed the D2 long receptor (D2LR) and D2 short receptor (D2SR). To study the function of these two isoforms an...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2004.04.005
更新日期:2005-04-01 00:00:00
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 Alzheim...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00135-5
更新日期:2003-05-01 00:00:00
abstract::Abnormal elevations in ammonia have been implicated in the pathogenesis of Alzheimer's disease. However, the biochemical mechanism(s) leading to increased ammonia in Alzheimer's disease have not yet been identified. A potential source of increased ammonia production is adenosine monophosphate (AMP) deaminase, an impor...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(98)00083-9
更新日期:1998-09-01 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::The available published guidelines for the housing of rodents are reviewed, and assessments are made with regard to whether the data on which these guidelines are based appear to be sound. Ambient air temperature, relative humidity, lighting levels and photoperiods, sound levels, cage sizes, and ventilation rates are ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,评审
doi:10.1016/0197-4580(91)90116-2
更新日期:1991-11-01 00:00:00
abstract::We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarrier...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.10.016
更新日期:2018-02-01 00:00:00
abstract::The effects of age were studied on a new animal model of tardive dyskinesia, i.e., the quantification of oral dyskinesia in rats repeatedly treated with reserpine. Adult and old rats received two injections of reserpine (0.5 or 1.0 mg/kg s.c.) or vehicle, separated by 48 h. One, 10, 25 and 40 days after the second inj...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(97)00152-8
更新日期:1997-11-01 00:00:00
abstract::Damaged mitochondria may be one of the earliest manifestations of Alzheimer's disease. Because oxidative phosphorylation is a primary source of neuronal energy, unlike glycolysis-dependent energy production in inflamed glia, mitochondrial respiration could provide a selective biomarker of neuronal deterioration in Alz...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.05.003
更新日期:2020-10-01 00:00:00
abstract::Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We invest...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.07.005
更新日期:2015-01-01 00:00:00
abstract::The etiology of Alzheimer's disease is still unknown. Because the disease is specific for human brain, a rational search for early diagnosis or prevention is very difficult. This calls for the development of cellular models that mimick the degeneration of neurons in AD. The brains of AD patients contain markers whose ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,评审
doi:10.1016/0197-4580(94)90178-3
更新日期:1994-01-01 00:00:00
abstract::This study modeled predementia Alzheimer's disease clinical trials. Longitudinal data from cognitively normal (CN) and mild cognitive impairment (MCI) participants in the Alzheimer's Disease Neuroimaging Initiative were used to calculate sample size requirements for trials using outcome measures, including the Clinica...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.03.006
更新日期:2013-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and, despite decades of effort, there is no effective treatment. In the last decade, many association studies have identified genetic markers that are associated with AD status. Two of these studies suggest that an epistatic interaction between variants rs1...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.01.013
更新日期:2020-05-01 00:00:00
abstract::Compared to young rats, old age increases susceptibility and caloric restriction decreases susceptibility for the loss of retinal ganglion cells and displaced amacrine cells following retinal ischemia/reperfusion. In retinas of old animals before ischemia, reactive gliosis, including activation of Muller cells, microg...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2003.07.005
更新日期:2004-04-01 00:00:00
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) to...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(99)00056-1
更新日期:1999-05-01 00:00:00
abstract:PURPOSE:The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. METHODS:16 C, 6 CI, and 7 D subjects of comparable age w...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00130-6
更新日期:2003-07-01 00:00:00
abstract::We have shown previously that the TG-3 and MPM-2 antibodies recognize phosphoepitopes common to mitosis and degenerating neurons of Alzheimer's disease(AD) brain. Here, we have evaluated their occurrence in human brain biopsy tissue, and confirm that they are absent in mature neurons of adult brain, but reappear durin...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(98)00071-2
更新日期:1998-07-01 00:00:00
abstract::The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2010.09.005
更新日期:2011-12-01 00:00:00