Abstract：
:Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding variant within the DNA methyltransferase gene DNMT3L (R278G, A/G) by examining B vitamin intake, homocysteine levels, cognitive performance, and brain atrophy in individuals in the VITACOG study of mild cognitive impairment and the TwinsUK cohort. In the VITACOG study, individuals who received a 2-year treatment of B vitamins and carried the G allele showed better "visuospatial associative memory" and slower rates of brain atrophy. In the TwinsUK study, improved "visuospatial associative memory" was evident in individuals who reported regular vitamin intake and were A/A homozygotes. In silico modeling indicated that R278G disrupts protein interaction between DNMT3L and DNMT3A, affecting the DNMT3A-3L-H3 complex required for DNA methylation. These findings show that vitamin intake and genetic variation within DNMT3L interact to influence cognitive decline.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Flitton M,Rielly N,Warman R,Warden D,Smith AD,Macdonald IA,Knight HMdoi
10.1016/j.neurobiolaging.2019.02.001subject
Has Abstractpub_date
2019-06-01 00:00:00pages
64-73eissn
0197-4580issn
1558-1497pii
S0197-4580(19)30041-7journal_volume
78pub_type
杂志文章abstract：:Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.11.009
更新日期：2018-03-01 00:00:00
abstract：:Pituitary-adrenal responsiveness to stress induced by either psychological (novelty) or physiological (ether) stimuli was examined in young (3 to 6 months) and old (24 to 27 months) male and female rats. In Experiment 1, subjects were placed in a novel environment for 3 min. Blood samples were collected at 0, 15, 30, ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(83)90037-4
更新日期：1983-07-01 00:00:00
abstract：:Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.04.004
更新日期：2016-10-01 00:00:00
abstract：:In order to investigate inflammation and apoptosis in Creutzfeldt-Jakob disease (CJD) patients, we analyzed astrocytes, microglia and apoptotic neurons in brain and IL-1beta in cerebrospinal fluid (CSF). Our results showed increased numbers of astrocytes in CJD and increased numbers of microglia and apoptotic neurons ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00236-6
更新日期：2002-01-01 00:00:00
abstract：:The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzh...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2017.03.001
更新日期：2017-08-01 00:00:00
abstract：:Since diabetes is a risk factor for Alzheimer's disease (AD), we asked if there is a functional interaction between high glucose and elevated beta amyloid peptide (Abeta) in cultured brain microvascular endothelial cells and presymptomatic AD transgenic mice. When cultured brain microvascular endothelial cells are exp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.02.010
更新日期：2009-12-01 00:00:00
abstract：:Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study exami...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.12.015
更新日期：2019-04-01 00:00:00
abstract：:In the aging mammalian hypothalamus, a unique subpopulation of glial cells accumulates peroxidase-positive cytoplasmic inclusions distinct from lipofuscin. In adult rodents, this senescence-dependent glial granulation is accelerated by administration of estradiol valerate. In the present study, brain sections derived ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)02018-7
更新日期：1995-11-01 00:00:00
abstract：:We identified neural correlates of declined and preserved basic visual attention functions in aging individuals based on Bundesen "Theory of Visual Attention". In an interindividual difference approach, we contrasted electrophysiology of higher- and lower-performing younger and older participants. In both age groups, ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.02.023
更新日期：2014-09-01 00:00:00
abstract：:APOE affects the risk of Alzheimer's disease (AD) and course of several other neurologic diseases. Experimental studies suggest that APOE influences synaptogenesis. We measured the concentration of two presynaptic proteins, synaptophysin and syntaxin 1, and also postsynaptic density-95 (PSD95), in superior temporal co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.04.008
更新日期：2006-06-01 00:00:00
abstract：:In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and tota...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.10.019
更新日期：2015-02-01 00:00:00
abstract：:Altered glutamate transport and aberrant EAAT1 expression were shown in Alzheimer's disease (AD) brains. It is presently unknown whether these modifications are a consequence of neurodegeneration or play a pathogenetic role. However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in AD platelets...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2004.07.007
更新日期：2005-06-01 00:00:00
abstract：:Plaques found in the brains of patients suffering from Alzheimer's disease (AD) mainly consist of beta-amyloid (Abeta), which is produced by sequential cleaving of amyloid precursor protein (APP) by two proteolytic enzymes, beta- and gamma-secretases. Any change in the fine balance between these enzymes and their subs...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.10.005
更新日期：2005-08-01 00:00:00
abstract：:Flavonoids, a group of dietary polyphenols have been shown to possess cognitive health benefits. Epidemiologic evidence suggests that they could play a role in risk reduction in dementia. Amyloid precursor protein processing and the subsequent generation of amyloid beta (Aβ) are central to the pathogenesis of Alzheime...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.032
更新日期：2015-01-01 00:00:00
abstract：:RACK1 (receptor for activated C-kinase 1), an anchoring protein that shuttles activated PKC to cellular membranes, plays an important role in PKC-mediated signal transduction pathways. A significant loss of RACK1 has been found in the brain of aging animals and Alzheimer's disease (AD) patients, which implicates the p...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.10.017
更新日期：2011-10-01 00:00:00
abstract：:Alzheimer's disease (AD) pathology has been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. A common LRRK2 Gly2385Arg variant has been widely shown to be associated with a twofold increased risk of PD in various Asian populations. In a case control study, the frequen...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.07.010
更新日期：2009-03-01 00:00:00
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 mon...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00230-0
更新日期：2003-10-01 00:00:00
abstract：:Modified forms of tau proteins are major components of the paired helical filaments (PHFs) present in Alzheimer brains. In this study, tau from cytosolic samples obtained from normal and Alzheimer disease brains were fractionated by iron-chelated affinity chromatography (ICAC) to discriminate between isoforms phosphor...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)00075-p
更新日期：1995-07-01 00:00:00
abstract：:Cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) were measured in aged (24 month) spontaneously hypertensive rats (SHR) during sodium nitroprusside (SNP) and nitroglycerin induced hypotension. Both CBF and CMRO2 were decreased in SHR during hypotension induced with SNP. Significant decrements in CMRO2 ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90003-3
更新日期：1982-07-01 00:00:00
abstract：:The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(96)00208-4
更新日期：1997-01-01 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 'amyloid hypothesis' has guided research into Alzheimer's disease (AD) for more than a decade. A detailed review of the relevant data led us to conclude that some data, particularly those from transgenic mice, are inconsistent with the predictions of the amyloid hypothesis. Instead, most data are consistent with t...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/s0197-4580(02)00050-7
更新日期：2002-11-01 00:00:00
abstract：:Using a dosing paradigm and an automated behavioral testing procedure designed to maximize potential drug efficacy, we evaluated the ability of clonidine to improve performance of aged monkeys on a trial-specific memory task. These results indicated that neither acutely administered (0.0025-0.04 mg/kg) or subchronical...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(88)80089-7
更新日期：1988-07-01 00:00:00
abstract：:Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present st...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00225-6
更新日期：2001-03-01 00:00:00
abstract：:Apolipoprotein E (APOE) ε4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all ε4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to ε4. A cognitively intact cohort (n = 932, age ≥ 75) was followed for 9 years to detect incid...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.03.003
更新日期：2013-01-01 00:00:00
abstract：:Energy deficiency and dysfunction of the Na,K-ATPase are common consequences of many pathological insults. Glutamate through cyclic GMP and cyclic GMP-dependent protein kinase (PKG) has been shown to stimulate alpha(2/3)-Na,K-ATPase activity in the central nervous system. Thus, a slight impairment of this pathway may ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.08.013
更新日期：2005-06-01 00:00:00
abstract：:The perimenopausal transition at middle age is often associated with hot flashes and sleep disruptions, metabolic changes, and other symptoms. Whereas the mechanisms for these processes are incompletely understood, both aging (AG) and a loss of ovarian estrogens play contributing roles. Furthermore, the timing of when...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.08.029
更新日期：2019-11-01 00:00:00
abstract：:Brains were examined from 22 patients with Alzheimer's disease (AD) (mean age 80.5, S.D. 11.5) and were compared with brains from 20 nondiseased subjects (mean age 81.1, S.D. 10.2). Intraneuronal lipopigment in all layers of a region of the superior frontal cortex was identified by fluorescence microscopy. The areas e...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90077-b
更新日期：1992-07-01 00:00:00
abstract：:White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessel disease, especially, in older age. Although significant sex differences have been reported in the severity of WMH, it is not yet known if the risk factors for WMH differ in men and women. In this study, magnetic re...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.11.001
更新日期：2020-11-10 00:00:00
abstract：:Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing condition...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2005.01.002
更新日期：2006-01-01 00:00:00
