Abstract:
:Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving motor neurons. Because a growing number of genes have been identified as the genetic etiology of ALS, simultaneous screening of mutations in multiple genes is likely to be more efficient than gene-by-gene testing. In this study, we performed a multigene panel testing by using targeted capture of 18 ALS-related genes followed by next-generation sequencing. Using this technique, we tried to identify mutations in 4 index patients with familial ALS and 148 sporadic ALS in Korean population and identified 4 known mutations in SOD1, ALS2, MAPT, and SQSTM1 genes, respectively, and 28 variants of uncertain significance in 9 genes. Among the 28 variants of uncertain significance, 6 missense variants were found in highly conserved residues and were consistently predicted to be deleterious by in silico analyses. These results suggest that multigene panel testing is an effective approach for mutation screening in ALS-related genes. Moreover, the relatively low frequency of mutations in known ALS genes implies marked genetic heterogeneity at least in Korean patients with ALS.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Kim HJ,Oh KW,Kwon MJ,Oh SI,Park JS,Kim YE,Choi BO,Lee S,Ki CS,Kim SHdoi
10.1016/j.neurobiolaging.2015.09.012subject
Has Abstractpub_date
2016-01-01 00:00:00pages
209.e9-209.e16eissn
0197-4580issn
1558-1497pii
S0197-4580(15)00469-8journal_volume
37pub_type
杂志文章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::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::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::Long-term dietary supplementation with resveratrol protects against cardiovascular disease, osteoporesis, and metabolic decline. This study determined how long-term dietary resveratrol treatment protects against retinal ganglion cell (RGC) dendrite loss after optic nerve injury and alters the resolution of the unfolde...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.12.021
更新日期:2015-05-01 00:00:00
abstract::To determine if the membrane disordering effect of ethanol on cerebral microvessels is altered with age, the steady state fluorescence polarization (P) of diphenyl-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) which report on the membrane core and surface region, respectively, ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90005-v
更新日期:1993-05-01 00:00:00
abstract::The effect of aging on exploratory behavior was investigated in adult (5 month) and aged (28 month) CB6F1 mice. During the first 10 minutes of the test session, aged mice made fewer head dip responses and spent less time exploring the novel stimuli. Because the aged mice were observed to subsequently increase their du...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(81)90021-x
更新日期:1981-10-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity in the adult brain and acute BDNF infusion has been shown to trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the effects of acute BDNF infusion in young adult and aged anesthetized rats. In young ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2004.01.003
更新日期:2004-11-01 00:00:00
abstract::To identify genes associated with frontotemporal dementia (FTD) in South-East Asia, targeted exome sequencing and C9orf72 genotyping was performed in 198 subjects (52 patients with FTD and 146 healthy controls) who were screened for mutations in 12 FTD-associated genes. We detected a homozygous TREM2 R47C mutation in ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.04.003
更新日期:2018-08-01 00:00:00
abstract::Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease pa...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.12.009
更新日期:2018-04-01 00:00:00
abstract::In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can i...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.10.014
更新日期:2016-02-01 00:00:00
abstract::Changes of performance monitoring during and after learning of stimulus-response (S-R) associations were examined in younger and older adults using event-related brain potentials (ERPs). To determine whether age-related differences in performance monitoring are attenuated when learning performance is equalized between...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2009.07.016
更新日期:2011-07-01 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
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::Amyotrophic lateral sclerosis (ALS) is a lethal neurological disease primarily involving the spinal cord, brainstem, and corticospinal tract. Recently, mutations in the GLE1 gene were reported in Caucasian ALS patients. To inquire whether Chinese ALS patients carried causal mutations in the gene, we screened all 16 co...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.12.029
更新日期:2018-06-01 00:00:00
abstract::We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilize...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2009.12.013
更新日期:2011-11-01 00:00:00
abstract::APOE-ε4 is a major genetic risk factor for late-onset Alzheimer's disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of APOE-ε4, family history (FH) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2020.06.014
更新日期:2020-10-01 00:00:00
abstract::The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, an...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2005.03.021
更新日期:2006-05-01 00:00:00
abstract::Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.10.023
更新日期:2018-03-01 00:00:00
abstract::The neurobiology of aging continues to attract scientists and techniques from the more fundamental disciplines, as witness the great strides now being made from molecular genetic approaches to Alzheimer's disease. The present report is a commentary on reviews of immune mechanisms and tissue culture methods applied to ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(88)80143-x
更新日期:1988-09-01 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::Deficits in synaptic structure and function are likely to underlie cognitive impairments in Alzheimer's disease. While synaptic deficits are commonly found in animal models of amyloidosis, it is unclear how amyloid pathology may impair synaptic functions. In some amyloid mouse models of Alzheimer's disease, however, s...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.07.009
更新日期:2016-11-01 00:00:00
abstract::The G4C2 hexanucleotide repeat expansion, located in the first intron of the C9ORF72 gene, represents a major genetic hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Several hypotheses have been proposed on how the transcribed repeat RNA leads to the development of amyotrophic lateral ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.09.012
更新日期:2015-02-01 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::Appreciation of the role that inflammatory mediators play in Alzheimer's disease (AD) pathogenesis continues to be hampered by two related misconceptions. The first is that to be pathogenically significant a neurodegenerative mechanism must be primary. The second is that inflammation merely occurs to clear the detriti...
journal_title:Neurobiology of aging
pub_type: 杂志文章,评审
doi:10.1016/0197-4580(96)00115-7
更新日期:1996-09-01 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::The injection of aluminum powder into the cerebrospinal fluid of adult rabbits induced a slowly progressing encephalomyelopathy characterized at first by alteration of posture and then by myoclonic jerks and muscle weakness. Neurofibrillary degeneration was the hallmark of the disease and involved most of the gray are...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(82)90041-0
更新日期:1982-10-01 00:00:00
abstract::A key question for the design of clinical trials for Alzheimer's disease (AD) is whether the timing of conversion from mild cognitive impairment (MCI) to AD can be predicted. This is also an important question for the clinical management of MCI. This study aims to address this question by exploring the contribution of...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.08.033
更新日期:2019-11-01 00:00:00
abstract::Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.10.004
更新日期:2017-02-01 00:00:00
abstract::Proceptive and receptive behaviors were examined in aging and young ovariectomized female rats treated with estradiol benzoate and progesterone. Young females approached males confined in wire mesh cages more frequently and exhibited more proceptive behaviors toward these males than did middle-aged females. Both middl...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(86)90038-2
更新日期:1986-05-01 00:00:00
abstract::This study examined the progression of sleep-disordered breathing (SDB) over 1 year in two samples of elderly subjects: 45 healthy controls (20 men; 25 women mean age 74.8 years) and 27 recently spousally bereaved elders (9 men; 18 women, mean age 69.7 years). Although controls and bereaved subjects did not differ in ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(92)90098-i
更新日期:1992-11-01 00:00:00