Abstract:
:Acetylcholinesterase (AChE) plays a crucial physiological role in termination of impulse transmission at cholinergic synapses through rapid hydrolysis of acetylcholine. In addition, it was implicated in amyloid plaque formation, a hallmark of Alzheimer's disease (AD), and most of the drugs used in AD treatment are AChE inhibitors. Thus ACHE is an obvious candidate gene for pharmacogenetic study of AD treatment. However, AChE is a highly conserved molecule, and only a few naturally occurring genetic polymorphisms have been reported in the human gene. The goals of this study were to make a systematic effort to identify natural single nucleotide polymorphisms (SNPs) in the human ACHE gene, and to reveal their population specific architecture. To this end, the genomic coding sequences for AChE of 96 unrelated control individuals from three distinct ethnic groups, African Americans, Ashkenazi Jews and Israeli Arabs, were analyzed. Thirteen ACHE SNPs were identified, ten of which are newly described, and five of which should produce amino-acid substitutions (Arg34Gln, Gly57Arg, Glu344Gly, His353Asn and Pro592Arg). Population frequencies of 11 of the 13 SNPs were established in four different populations, African Americans, Ashkenazi Jews, Sephardic Jews and Israeli Arabs; 17 haplotypes and 5 ethno-specific alleles were identified, and a cladogram of ACHE haplotypes was constructed. Among the SNPs resulting in an amino-acid substitution, three are within the mature protein, mapping on its external surface; they are thus unlikely to affect its catalytic properties, yet could have antigenic consequences or affect putative protein-protein interactions. Furthermore, the newly identified SNPs open the door to a study of the possible association of AChE with deleterious phenotypes - such as adverse drug responses to AChE inhibitors employed in treatment of AD patients and hypersensitivity to pesticides.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
Hasin Y,Avidan N,Bercovich D,Korczyn AD,Silman I,Beckmann JS,Sussman JLdoi
10.2174/1567205053585909keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
207-18issue
2eissn
1567-2050issn
1875-5828journal_volume
2pub_type
杂志文章abstract:BACKGROUND:Various methodologies have been employed for the localization of amyloid plaques in numerous studies on Alzheimer's disease. The majority of these stains are thought to label the plaques by virtue of their affinity for aggregated Aβ. However, plaques are known to contain numerous other components, including ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190725155038
更新日期:2019-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder linked to protein misfolding and aggregation. AD is pathologically characterized by senile plaques formed by extracellular Amyloid-β (Aβ) peptide and Intracellular Neurofibrillary Tangles (NFT) formed by hyperphosphorylated tau protein. Extensive synaptic loss a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205016666190321163438
更新日期:2019-01-01 00:00:00
abstract::The remarkable potentiality of bone marrow-derived mesenchymal stem cells (BM-MSCs) after transplantation to models of neurological disease and injury has been described. We have previously published data confirming the influence of BM-MSCs on β-amyloid (Aβ) deposition in an Alzheimer's disease (AD) mouse model. Howev...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) is the most widely used cognitive outcome measure in AD trials. Although errors in administration and scoring have been suggested as factors masking accurate estimates and potential effects of treatments, there have been few formal exam...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795745357
更新日期:2011-06-01 00:00:00
abstract::Evidence from basic molecular biology has noted a critical role of GSK-3 in Alzheimer's disease (AD) pathogenesis such as beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangle (NFT), and neuronal degeneration. Aβ generation and deposition represents a key feature and is generated from ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720512802455386
更新日期:2012-09-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder among the elderly. Nmethyl- D-aspartate receptor (NMDAR) overactivation has been implicated in early synaptic dysfunction that precedes late neurodegeneration in AD. Moreover, oligomers of amyloid-beta peptide (Aβ) 1-42 are considered t...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512802455322
更新日期:2012-09-01 00:00:00
abstract::The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795255982
更新日期:2011-03-01 00:00:00
abstract::Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer's disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids t...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205015666180911151716
更新日期:2018-01-01 00:00:00
abstract::Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in the Morris water maze, a hippocampal-dependent learning task, leads to an increase in local VEGF expres...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506775697133
更新日期:2006-02-01 00:00:00
abstract::Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD). The main endogenous antioxidant, glutathione (GSH), has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH level...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150302160308
更新日期:2015-01-01 00:00:00
abstract::Anesthesia and surgery have been reported to produce long-term cognitive problems, and to accelerate neurodegenerative disorders in the elderly. In previous work, we found that inhaled anesthetics enhance fibril formation and cytotoxicity of amyloid beta peptide. In this work we show that the inhaled anesthetics halot...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720507781077278
更新日期:2007-07-01 00:00:00
abstract::To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimer's type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed t...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720505774932223
更新日期:2005-12-01 00:00:00
abstract:INTRODUCTION:Histaminergic H3 receptors may play a role in modulating cholinergic and monoaminergic neurotransmission. This Phase II study evaluated the efficacy and safety of GSK239512, a highly potent, brain penetrant H3 receptor antagonist as monotherapy treatment for subjects with mild-to-moderate probable Alzheime...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/1567205010666131212110148
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Increasing basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of Alzheimer's Disease. Excess TNF-alpha, a cytokine with pleotropic effects in the CNS, has been suggested to be involved in the pathogenesis of AD. In addition to its pro-infl...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507783018217
更新日期:2007-12-01 00:00:00
abstract::Mutations in presenilin 1 (PS1) cause early-onset familial Alzheimer;s disease (FAD). Although FAD accounts for less than 5% of all cases of Alzheimer;s disease (AD), extensive analyses of PS1 function have elucidated an important neuronal mechanism underling AD pathogenesis. PS1 is considered to be an essential compo...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205043480528
更新日期:2004-02-01 00:00:00
abstract::Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720510793499075
更新日期:2010-11-01 00:00:00
abstract::Accumulating evidence has suggested the involvement of oxidative stress in the pathogenesis of Alzheimer's disease (AD).The main endogenousantioxidant,glutathione (GSH),has been shown to decline with ageing and in several age-related degenerative diseases, including AD. Potential options for replenishing GSH levels as...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2015-03-24 00:00:00
abstract::In the last decade, several radiolabeled compounds have been developed for the imaging in vivo of amyloid pathology by means of Positron Emission Tomography (PET). Among these, 18F Florbetaben appear to be one of the most reliable for its high affinity for amyloid plaques in brain and its radio-chemical properties tha...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160620114309
更新日期:2017-01-01 00:00:00
abstract::Alzheimer's disease (AD) is currently the most prominent form of dementia among the elderly. Although AD manifests in late adult life, it is not clear when the disease actually starts and how long the neuropathological processes take to develop AD. The major unresolved question is the timing and the nature of triggeri...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362164
更新日期:2007-04-01 00:00:00
abstract::Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneratio...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205012666150921095505
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to det...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666141001120903
更新日期:2014-01-01 00:00:00
abstract::The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effe...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140505094808
更新日期:2014-01-01 00:00:00
abstract::A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, suc...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720511795745276
更新日期:2011-06-01 00:00:00
abstract::What are the resources needed by clinical pharmacology to test drugs in ways that model how the practitioner achieves optimal effectiveness and safety with each patient? I describe the applications of test-retest standard error of measurement, clinical decision rules, means or other statistical summaries of observatio...
journal_title:Current Alzheimer research
pub_type: 历史文章,杂志文章,评审
doi:10.2174/156720507781788828
更新日期:2007-09-01 00:00:00
abstract::At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important f...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720511796391818
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarme...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190228124630
更新日期:2019-01-01 00:00:00
abstract::Human memory can be split into familiarity and recollection processes which contribute to different aspects of memory function. These separate processes result in different experiential states. In this review, we examine how this dominant theoretical framework can explain the subjective experience of people with Alzhe...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509788486545
更新日期:2009-06-01 00:00:00
abstract::Recent studies have shown that the translocase of outer mitochondrial membrane 40 homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which is associated with an increase in AD incidence among APOE 3 carriers. Current methods to isotype the poly-T region rely on long PCR, subcloning and sequenc...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512804142921
更新日期:2012-12-01 00:00:00
abstract::With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in communi...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720501108140910123112
更新日期:2014-01-01 00:00:00
abstract::Amyloid-β protein (Aβ) accumulates in the neurons of Alzheimer's disease (AD) patients at an early stage of the disease. Recently, we found that Aβ with a toxic turn at positions 22 and 23 accumulates in neurons in AD brain. Here, we studied the accumulation of Aβ, toxic turn Aβ and high-molecular-weight Aβ oligomers ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00