Abstract:
:Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2 [conditioned medium] CM) Aβ-induced deficits in synaptic plasticity and learned behavior was assessed. Biochemically, SEN1500 bound to Aβ monomer and oligomers, produced a reduction in thioflavin-T fluorescence, and protected a neuronal cell line and primary cortical neurons exposed to synthetic soluble oligomeric Aβ(1-42). Electrophysiologically, SEN1500 alleviated the in vitro depression of long-term potentiation induced by both synthetic Aβ(1-42) and 7PA2 CM, and alleviated the in vivo depression of long-term potentiation induced by 7PA2 CM, after systemic administration. Behaviorally, oral administration of SEN1500 significantly reduced memory-related deficits in operant responding induced after intracerebroventricular injection of 7PA2 CM. SEN1500 reduced cytotoxicity, acute synaptotoxicity, and behavioral deterioration after in vitro and in vivo exposure to synthetic Aβ and 7PA2 CM, and shows promise for development as a clinically viable disease-modifying Alzheimer's disease treatment.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
O'Hare E,Scopes DI,Kim EM,Palmer P,Jones M,Whyment AD,Spanswick D,Amijee H,Nerou E,McMahon B,Treherne JM,Jeggo Rdoi
10.1016/j.neurobiolaging.2012.10.016subject
Has Abstractpub_date
2013-04-01 00:00:00pages
1116-25issue
4eissn
0197-4580issn
1558-1497pii
S0197-4580(12)00527-1journal_volume
34pub_type
杂志文章abstract::Hippocampal atrophy rates are useful in both diagnosing and tracking Alzheimer's disease (AD). However, cohorts and methods used to determine such rates are heterogeneous, leading to differences in reported annualised rates. We performed a meta-analysis of hippocampal atrophy rates in AD patients and matched controls ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.neurobiolaging.2008.01.010
更新日期:2009-11-01 00:00:00
abstract::Differential cell death is a common feature of aging and age-related disease. In the retina, 30% of rod photoreceptors are lost over life in humans and rodents. However, studies have failed to show age-related cell death in mouse cone photoreceptors, which is surprising because cone physiological function declines wit...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.05.012
更新日期:2014-11-01 00:00:00
abstract::A study on familial Parkinson disease (PD) described 4 variants in the gene TMEM230 (Chr. 20p13) as the cause of PD. The aim of this study was to test if variants in the TMEM230 gene are associated with PD in 2 independent American European data sets. No variants in the TMEM230 region were found associated with PD, ag...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.03.014
更新日期:2017-08-01 00:00:00
abstract::The majority (90%-95%) of amyotrophic lateral sclerosis (ALS) is sporadic, and ∼50% of patients develop symptoms of frontotemporal degeneration (FTD) associated with shorter survival. The genetic polymorphism rs12608932 in UNC13A confers increased risk of sporadic ALS and sporadic FTD and modifies survival in ALS. Her...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.09.031
更新日期:2019-01-01 00:00:00
abstract::In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkin...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.05.026
更新日期:2018-09-01 00:00:00
abstract::To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-epsilon4 allele was the strongest risk factor, and with increasing survival age, the effect of...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2004.04.010
更新日期:2005-03-01 00:00:00
abstract::The 3-dimensional (3-D) distribution of cholinergic neurons located throughout the extent of the entire basal forebrain of young (4-5 months old) and aged (24-25 months old) Fischer-344 rats was examined using choline acetyltransferase immunocytochemistry (ChAT-IR). The number and 3-D position of ChAT-IR neurons spann...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90126-v
更新日期:1993-07-01 00:00:00
abstract::The present study was designed to examine the effects of the aging process on the response of motoneurons to axotomy. Accordingly, in aged cats using intracellular recording techniques, the electrophysiological properties of axotomized lumbar spinal cord motoneurons were compared with those of control (nonaxotomized) ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(92)90035-v
更新日期:1992-03-01 00:00:00
abstract::CR1 is a novel Alzheimer's disease (AD) gene identified by genome-wide association studies (GWAS). Recently, we showed that AD risk could be explained by an 18-kilobase insertion responsible for the complement component (3b/4b) receptor 1 (CR1)-S isoform. We investigated the relevance of the CR1 isoforms to AD in a Ca...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.07.001
更新日期:2012-12-01 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::Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine da...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90029-b
更新日期:1993-01-01 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::Iron is essential for triggering oligodendrocytes to myelinate, however, in gray matter (GM) iron increases with age and is associated with age-related degenerative brain diseases. Women have lower iron levels than men, both in the periphery and in the brain, particularly in white matter (WM), possibly due to iron los...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2011.08.002
更新日期:2012-09-01 00:00:00
abstract::While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional informati...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.08.018
更新日期:2017-01-01 00:00:00
abstract::The apolipoprotein E (ApoE) ε4 allele has consistently been established as an Alzheimer's disease (AD) risk factor, but its pathological contribution to AD is obscure. Certain butyrylcholinesterase (BuChE) polymorphisms together with the ApoE ε4 allele synergistically increase the risk of AD. In addition, AD risk fact...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2009.07.015
更新日期:2011-07-01 00:00:00
abstract::Multiple degenerative hallmarks characterize Alzheimer's disease: insoluble protein deposition, neuronal loss and cortical atrophy. Atrophy begins in the medial temporal lobe and becomes global by end stage. In a small proportion of cases, these tissue changes are caused by mutations in three known genes. These cases ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2005.03.011
更新日期:2006-03-01 00:00:00
abstract::Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::Progranulin (GRN) gene mutations have been genetically associated with frontotemporal dementia (FTD) and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of 3 pedigrees of Southern Italian extraction in w...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.12.030
更新日期:2017-05-01 00:00:00
abstract::Eight elderly subjects (aged 68-95 years) and 6 young adults (aged 21-24 years) performed elbow flexion and extension movements in a visual step-tracking paradigm. Movement amplitudes ranging from 10 degrees-80 degrees were made under two instructions: "move at own speed" and "move fast and accurate." In a second expe...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(89)90024-9
更新日期:1989-03-01 00:00:00
abstract:OBJECTIVE:To determine the patterns of cerebral glucose metabolism in frontotemporal dementia (FTD) and semantic dementia (SD). METHODS:25 patients with mild FTD and 9 patients with mild SD as well as 15 healthy age-matched control subjects underwent 18F-FDG- positron emission tomography. Patient scans were compared w...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2003.10.007
更新日期:2004-09-01 00:00:00
abstract::Next-generation sequencing was used to investigate 9 rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. Five probands with ataxia-telangectasia and 1 proband with chorea-acanthocytosis were analyzed by targeted gene sequencing. Whole-exome sequencing was used to investigate 3 affected...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.04.029
更新日期:2013-10-01 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::Cholesterol is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholestero...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.09.040
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVE:We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD:Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously...
journal_title:Neurobiology of aging
pub_type: 临床试验,杂志文章
doi:10.1016/j.neurobiolaging.2004.03.003
更新日期:2005-02-01 00:00:00
abstract::Amyloid beta (Aβ) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Alpha-cleavage of APP by α-secretase has a potential to preclude the generation of Aβ because it occurs within the A...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.07.014
更新日期:2014-01-01 00:00:00
abstract::The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the oth...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(95)02074-8
更新日期:1996-03-01 00:00:00
abstract::Threshold and suprathreshold sensitivities to 13 bitter compounds were determined for 16 young adults (mean age = 27.4 years) and 18 elderly persons (mean age = 81.3 years). Half of the subjects in each age group were tasters of the bitter compound phenylthiocarbamide (PTC) and half were nontasters. Both detection and...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(94)90057-4
更新日期:1994-11-01 00:00:00
abstract::In Pick disease and progressive supranuclear palsy (PSP), accumulations of phosphorylated tau are associated with oxidative stress, although the mechanism linking these features remains unknown. However, we suspected that the oxidative stress-induced activation of mitogen-activated protein kinases might lead to tau ph...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00029-5
更新日期:2002-09-01 00:00:00
abstract::Changes in regional cerebral blood flow (rCBF) associated with a face-matching task were examined using positron emission tomography (PET) and H2(15)O in 7 patients with mild-moderate dementia of the Alzheimer type (DAT) and in 8 healthy age-matched controls. rCBF was normalized to whole brain flow and pixel-by-pixel ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90018-7
更新日期:1993-01-01 00:00:00
abstract::This study investigated the role of genetic and environmental influences on individual differences in brain volumes measured at 2 time points in normal elderly males from the National Heart, Lung, and Blood Institute Twin Study. The magnetic resonance imaging (MRI) scans were conducted 4 years apart on 33 monozygotic ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,多中心研究
doi:10.1016/j.neurobiolaging.2010.06.002
更新日期:2012-04-01 00:00:00