Abstract：
:Genome-wide association studies have associated clusterin (CLU) variants with Alzheimer's disease (AD). However, the role of CLU on AD pathogenesis is not totally understood. We used cerebrospinal fluid (CSF) and plasma CLU levels as endophenotypes for genetic studies to understand the role of CLU in AD. CSF, but not plasma, CLU levels were significantly associated with AD status and CSF tau/amyloid-beta ratio, and highly correlated with CSF apolipoprotein E (APOE) levels. Several loci showed almost genome-wide significant associations including LINC00917 (p = 3.98 × 10(-7)) and interleukin 6 (IL6, p = 9.94 × 10(-6), in the entire data set and in the APOE ε4- individuals p = 7.40 × 10(-8)). Gene ontology analyses suggest that CSF CLU levels may be associated with wound healing and immune response which supports previous functional studies that demonstrated an association between CLU and IL6. CLU may play a role in AD by influencing immune system changes that have been observed in AD or by disrupting healing after neurodegeneration.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Deming Y,Xia J,Cai Y,Lord J,Holmans P,Bertelsen S,Holtzman D,Morris JC,Bales K,Pickering EH,Kauwe J,Goate A,Cruchaga C,Alzheimer's Disease Neuroimaging Initiative (ADNI).doi
10.1016/j.neurobiolaging.2015.09.009subject
Has Abstractpub_date
2016-01-01 00:00:00pages
208.e1-208.e9eissn
0197-4580issn
1558-1497pii
S0197-4580(15)00466-2journal_volume
37pub_type
杂志文章abstract：:Previous electrophysiological studies in aged rats have revealed a number of deficits in noradrenergic neurotransmission in the central nervous system. Such deficits include subsensitivity to the depressant effects of norepinephrine on cerebellar Purkinje neurons, which has been attributed specifically to altered beta...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90022-r
更新日期：1990-11-01 00:00:00
abstract：:There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast admini...
journal_title：Neurobiology of aging
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.neurobiolaging.2019.01.014
更新日期：2019-05-01 00:00:00
abstract：:Data are emerging that the altered development of adrenocortical and emotional reactivity in individuals exposed perinatally to adverse events is reflected in cognitive change and that maternal care is an important determinant. However, early trauma does not cause a generalized cognitive decline at older age, but rath...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/s0197-4580(03)00057-5
更新日期：2003-05-01 00:00:00
abstract：:Anticholinergic drug use is common in older adults and has been related to increased dementia risk. This suggests that users of these drugs may experience accelerated cognitive decline. So far, however, longitudinal data on this topic are absent and the available evidence is inconclusive with respect to effects on spe...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.03.009
更新日期：2017-07-01 00:00:00
abstract：:Demonstrations that grip strength has predictive power in relation to a range of health conditions-even when these are assessed decades later-has motivated claims that hand-grip dynamometry has the potential to serve as a "vital sign" for middle-aged and older adults. Central to this belief has been the assumption tha...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2018.07.023
更新日期：2018-11-01 00:00:00
abstract：:Although senile plaques represent a consistent neuropathological feature in Alzheimer's brains, it is not known what role plaques play in the etiology of the disease. Both growth-promoting and growth-inhibiting influences have been postulated. One of the major components in plaques, beta-amyloid, has been shown to aff...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90002-s
更新日期：1993-05-01 00:00:00
abstract：:The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object reco...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.04.003
更新日期：2012-03-01 00:00:00
abstract：:In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)97327-d
更新日期：1995-05-01 00:00:00
abstract：:As a major characteristic of aging process, neuroinflammation is involved in the pathogenesis of several aging-related diseases including Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a newly identified risk gene for AD, which regulates inflammatory process in peripheral tissues...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.11.026
更新日期：2014-06-01 00:00:00
abstract：:While resting, Fischer-344 rats underwent a decrease in heart rate and an increase in diastolic blood pressure and plasma norepinephrine with increasing age. The blood pressure of adult rats increased significantly during a 3 minute immobilization. The blood pressure of old rats failed to increase during stress, decre...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(80)90010-x
更新日期：1980-01-01 00:00:00
abstract：:An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challeng...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.008
更新日期：2016-10-01 00:00:00
abstract：:Synaptic failure underlies cognitive impairment in Alzheimer's disease (AD). Cumulative evidence suggests a strong link between mitochondrial dysfunction and synaptic deficits in AD. We previously found that oligomycin-sensitivity-conferring protein (OSCP) dysfunction produces pronounced neuronal mitochondrial defects...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.09.018
更新日期：2020-10-16 00:00:00
abstract：:Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.08.011
更新日期：2009-05-01 00:00:00
abstract：:Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T(2)-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically nor...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.05.013
更新日期：2009-01-01 00:00:00
abstract：:Oxidative stress is believed to be a significant cause of Parkinson's disease (PD). DJ-1 is thought to be an oxidative sensor that protects cells from oxidative insult. It was reported that the level of total DJ-1 protein was significantly reduced in the substantia nigra of sporadic PD patients, suggesting that abnorm...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.09.027
更新日期：2014-03-01 00:00:00
abstract：:Hearing impairment in older people is thought to arise from impaired temporal processing in auditory circuits. We used a systems-level (scalp recordings) and a microcircuit-level (extracellular recordings) approach to investigate how aging affects the sensitivity to temporal envelopes of speech-like sounds in rats. Sc...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.08.023
更新日期：2019-01-01 00:00:00
abstract：:Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they associate with cholesterol concentrations and, for rs6084, coronary artery disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent e...
journal_title：Neurobiology of aging
pub_type： 杂志文章,多中心研究
doi：10.1016/j.neurobiolaging.2006.11.015
更新日期：2008-05-01 00:00:00
abstract：:Age-related macular degeneration (AMD) has been linked to memory deficits, with no established neural mechanisms. We collected resting-state brain functional magnetic resonance imaging and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.07.020
更新日期：2020-11-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.01.004
更新日期：2017-05-01 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：:Linkage data in Alzheimer's disease have not firmly established a genetic locus on chromosome 21 in early onset disease families. There is little or no support for a chromosome 21 locus in late onset families. Differences in the selection of families and the analysis of data accounts for the differences in interpretat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90083-3
更新日期：1989-09-01 00:00:00
abstract：:Early manifestations of brain aging have received much less attention than the drastic degeneration of AD and MID. During nonpathological changes of normal aging, brain systems differ in the involvement of neuron loss. Spatial learning can become impaired without evidence for neuron loss, whereas eye-blink conditionin...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(03)00051-4
更新日期：2003-05-01 00:00:00
abstract：:Acetyl-1-carnitine (AC) was administered via drinking water for six months to one group (OLD-AC) of male F-344 rats beginning at 16 months of age, while another group (OLD-CON) of rats was given water only during that period. The rats were maintained on this treatment throughout behavioral testing, which began at 22 m...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90110-l
更新日期：1990-09-01 00:00:00
abstract：:Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.12.009
更新日期：2014-06-01 00:00:00
abstract：:Recent studies have implicated increased oxidative stress in the pathogenesis of Alzheimer's disease (AD). Increased lipid peroxidation and decreased polyunsaturated fatty acid levels have been described in the brain in AD. Four-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been demonstrated to ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00009-8
更新日期：1998-01-01 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：:Reduced excitability, due to an increase in the slow afterhyperpolarization (and its underlying current sI(AHP)), occurs in CA1 pyramidal cells in aged cognitively-impaired, but not cognitively-unimpaired, rodents. We sought to determine whether similar age-related changes in the sI(AHP) occur in pyramidal cells in th...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.07.002
更新日期：2012-06-01 00:00:00
abstract：:Alzheimer's disease (AD) is generally considered to be a disorder primarily affecting memory. It is increasingly recognized that the clinical presentation or "cognitive phenotype" is variable. The apolipoprotein E ε4 (APOE ε4) allele has been associated with an amnestic presentation, but does not appear to fully expla...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.11.003
更新日期：2012-07-01 00:00:00
abstract：:The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(86)90055-2
更新日期：1986-11-01 00:00:00
abstract：:Flexible instrumental learning is required to harness the appropriate behaviors to obtain rewards and to avoid punishments. The precise contribution of dopaminergic midbrain regions (substantia nigra/ventral tegmental area [SN/VTA]) to this form of behavioral adaptation remains unclear. Normal aging is associated with...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.030
更新日期：2013-10-01 00:00:00
