Abstract：
:Mutations in Leucine-rich repeat kinase 2 (LRRK2) are recognized as the most frequent genetic factors contributing to Parkinson's disease (PD). The aim of our study was to explore LRRK2 variants in PD patients within the mainland Han Chinese population. The whole coding regions of LRRK2 from 296 PD patients were sequenced by targeted regions sequencing and exome sequencing. Eighteen rare variants were identified in 27 PD patients, and 13 of them (M100T, L153W, A459S, S722N, R792K, C925Y, R981K, S1007T, V1447M, R1677S, N2308D, N2313S, and S2350I) were firstly reported in PD. We also tried to explore the genotype-phenotype associations of LRRK2 variants in our data and found that PD with common and rare LRRK2 variants was more likely to have motor fluctuation and nonmotor symptoms. The identification of novel variants in LRRK2 suggests that this gene plays an important role in the pathogenesis and phenotype of PD in Han Chinese population, and our data also rang the alarm bell-more attention should be paid to the whole coding regions of LRRK2.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Zhang JR,Jin H,Li K,Mao CJ,Yang YP,Wang F,Gu CC,Zhang HJ,Chen J,Liu CFdoi
10.1016/j.neurobiolaging.2018.06.036subject
Has Abstractpub_date
2018-12-01 00:00:00pages
187.e5-187.e10eissn
0197-4580issn
1558-1497pii
S0197-4580(18)30241-0journal_volume
72pub_type
杂志文章abstract：:Estrogens have been implicated as possible therapeutic agents for improving cognition in postmenopausal women and have been linked to neurodegenerative disorders such as Alzheimer's disease. However, the utility of Premarin (Wyeth Pharmaceuticals, Markham, ON, Canada), a conjugated equine estrogen and the most commonl...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.07.009
更新日期：2013-03-01 00:00:00
abstract：:We previously found a selective loss of the brain specific APP-695 transcript in Alzheimer's disease (AD) cortex, which results in a 2.5-fold increase in the APP-751/APP-695 transcript ratio in AD (9). Here we report a similar increase in APP-751/APP-695 mRNA ratio in AD hippocampus. However, the cerebellum had a 6-fo...
journal_title：Neurobiology of aging
pub_type： 更正并重新发布的文章,杂志文章
doi：10.1016/0197-4580(89)90017-1
更新日期：1989-11-01 00:00:00
abstract：:Accumulating evidence suggests that the propagation of hyperphosphorylation of tau protein and the amyloid-β peptide can be mediated by extracellular vesicles (EVs) and be associated with the onset and the progression of Alzheimer's disease (AD). As EVs may transfer between the brain and the blood, we have thus hypoth...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.10.010
更新日期：2020-02-01 00:00:00
abstract：:Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.012
更新日期：2012-09-01 00:00:00
abstract：:Neurokinin B and its cognate neurokinin-3 receptor are expressed more in the forebrain than in brain stem structures but little is known about the primary function of this peptide system in the central processing of information. In general, few studies have specifically addressed age-related changes of tachykinins, no...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(99)00019-6
更新日期：1999-01-01 00:00:00
abstract：:Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over- or underexpress neuregulin-1 (NRG1), a direct ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.05.011
更新日期：2011-12-01 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：:Mutants of presenilin 1 (PS1) increase neuronal cell death causing autosomal-dominant familial Alzheimer's disease (FAD). Recent literature shows that treatment of neuronal cultures with low concentrations of trypsin, a member of the serine family of proteases, protects neurons from toxic insults by binding to the pro...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.028
更新日期：2016-06-01 00:00:00
abstract：:Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinic...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.11.005
更新日期：2013-05-01 00:00:00
abstract：:Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease caused by an abnormal expansion of a tandem CAG repeat in exon 1 of the androgen receptor (AR) gene that results in an abnormally long polyglutamine tract (polyQ) in the AR protein. As a result, the mutant AR (ARpolyQ) misfolds, forming cytopl...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.05.026
更新日期：2013-11-01 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：:Parkinson's disease (PD) is a progressive neurodegenerative disease with typical motor symptoms due to the preferential loss of midbrain dopaminergic (mDA) neurons in the Substantia nigra pars compacta. Several proteins of the homeodomain family are crucial for the development of mDA neurons. These proteins remain exp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.08.014
更新日期：2009-05-01 00:00:00
abstract：:The ability to perceive and produce speech undergoes important changes in late adulthood. The goal of the present study was to characterize functional and structural age-related differences in the cortical network that support speech perception and production, using magnetic resonance imaging, as well as the relations...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.02.004
更新日期：2013-08-01 00:00:00
abstract：:Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90087-z
更新日期：1991-09-01 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 effects of age were studied on a new animal model of tardive dyskinesia, i.e., the quantification of oral dyskinesia in rats repeatedly treated with reserpine. Adult and old rats received two injections of reserpine (0.5 or 1.0 mg/kg s.c.) or vehicle, separated by 48 h. One, 10, 25 and 40 days after the second inj...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00152-8
更新日期：1997-11-01 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：:While cytoskeletal abnormalities are prominent in the neurons of patients with Alzheimer's disease, the possibility remains that these changes are secondary to changes in the neuronal environment. The success of NGF in the therapy of Alzheimer's disease may be dependent on its ability to promote neuronal survival rath...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90134-6
更新日期：1989-09-01 00:00:00
abstract：:Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (Neur...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.038
更新日期：2015-01-01 00:00:00
abstract：:We conducted genetic analysis of the fused in sarcoma gene (FUS) in Chinese Han patients with essential tremor (ET) in a case-control association study. One hundred eighty unrelated patients with ET were screened for mutations in the coding region and exon-intron boundaries of FUS. Reverse transcriptase polymerase cha...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.001
更新日期：2013-08-01 00:00:00
abstract：:The levels of calpains (m-calpain and mu-calpain) in peripheral blood lymphocytes from patients with Alzheimer's disease were determined via Western blotting. The Ca-dependent proteolytic activity and the calpastatin activity were estimated using incubation with exogenous substrate. Evidence was obtained for an increa...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)02004-7
更新日期：1995-11-01 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：:These studies were designed to assess some of the morphological alterations that occur in medium-sized spiny neurons of the caudate nucleus in aged cats. Computer assistance was used to quantify in three dimensions the extent of the dendritic trees of 164 neurons from 11 cats (5 1-3 years and 6 over 10 years of age) s...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(86)90008-4
更新日期：1986-07-01 00:00:00
abstract：:Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study,...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.023
更新日期：2012-05-01 00:00:00
abstract：:The overall goal was to identify patterns of brain atrophy associated with cognitive impairment and future cognitive decline in non-demented elders. Seventy-one participants were studied with structural MRI and neuropsychological testing at baseline and 1-year follow-up. Deformation-based morphometry was used to exami...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.04.011
更新日期：2011-04-01 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：:Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therap...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.016
更新日期：2012-06-01 00:00:00
abstract：:The Asp620Asn mutation in the vacuolar protein sorting protein 35 (VPS35) gene and the Arg1205His mutation in the eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) gene were identified in autosomal dominant late-onset familial and sporadic Parkinson disease (PD) patients in a Caucasian population. However, t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.11.003
更新日期：2013-06-01 00:00:00
abstract：:We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early-stage Alzheimer's disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy, and dementia progression. Individuals with early-stage AD (n = 37) and without dementia (...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.03.016
更新日期：2012-08-01 00:00:00
abstract：:Four biopsies of the brain cortex of patients with Alzheimer's disease were used for ultrastructural studies. Three-dimensional reconstruction and morphometric studies of three classical plaques were carried out to determine the distribution of the astrocytes and their processes, and spatial relationships between astr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90091-w
更新日期：1991-09-01 00:00:00
