Abstract：
:Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Oeda T,Umemura A,Mori Y,Tomita S,Kohsaka M,Park K,Inoue K,Fujimura H,Hasegawa H,Sugiyama H,Sawada Hdoi
10.1016/j.neurobiolaging.2015.08.027subject
Has Abstractpub_date
2015-12-01 00:00:00pages
3306-3313issue
12eissn
0197-4580issn
1558-1497pii
S0197-4580(15)00444-3journal_volume
36pub_type
杂志文章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：:The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R vari...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.03.029
更新日期：2016-07-01 00:00:00
abstract：:Recent findings seem to converge towards a unified hypothesis trying to relate Down's syndrome (DS), trisomy 21 and Alzheimer's disease (AD). The majority of DS individuals develop neuropathological characteristics of AD by the age of 40. Previous cytogenetic studies performed by us showed an increased frequency of an...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.025
更新日期：2006-05-01 00:00:00
abstract：:Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPα) having neuroprotective properties and the beta amyloid (Aβ) peptide at the origin of neurotoxic oligomers, particularly Aβ1-42. Whether extracellular Aβ1-42 oligomers m...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.09.008
更新日期：2018-01-01 00:00:00
abstract：:Age at the time of brain injury is generally considered an important determinant in recovery of function. The implication is that older individuals show less recovery. Existing data challenge this common notion, but suggest differential effects of brain damage in aged subjects. To assess these differences old rats wer...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(83)90018-0
更新日期：1983-10-01 00:00:00
abstract：:Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the 2 most common causes of dementia. We compared the regional metabolism on 18F-fluorodeoxyglucose positron emission tomography (PET) among 21 control subjects and cognitively impaired patients due to DLB (N = 63) and AD (N = 38). All participants under...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.10.020
更新日期：2020-03-01 00:00:00
abstract：:Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and age...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.07.004
更新日期：2004-07-01 00:00:00
abstract：:Decreased levels of cerebrospinal fluid (CSF) Abeta42 is a diagnostic marker of Alzheimer's disease. To clarify the biological basis of this marker, the physiological alterations of CSF Abeta40 and Abeta42 by aging were studied. CSF samples from 92 normal subjects between 8 and 89 years old were measured using a speci...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00229-3
更新日期：2001-03-01 00:00:00
abstract：:We designed this study to determine whether the sexual behavior of male monkeys changes on a diurnal schedule that coincides with changes in the levels of hormones such as luteinizing hormone (LH), testosterone, estradiol, and cortisol, and whether these differences vary with age. Old (n = 8) and young (n = 8) males w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90059-8
更新日期：1982-04-01 00:00:00
abstract：:Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophin. However, its role in human Alzheimer's disease (AD) is largely unknown. We examined PACAP expression in postmortem human AD and triple transgenic mouse (3xTG, Psen1/APPSwe/TauP301L) brains. We established an in vitro model of primary neurona...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.022
更新日期：2014-09-01 00:00:00
abstract：:After a decade of intense study of cholinergic therapies for Alzheimer's disease, three conditions in this field are apparent: 1) The potential that cholinergic agents will ameliorate the memory dysfunction of Alzheimer patients (as 1-dopa benefits Parkinson patients) is still a stimulus for research. 2) Cholinergic n...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(89)80017-x
更新日期：1989-01-01 00:00:00
abstract：:Macrophages or activated microglia in the subretinal space are considered a hallmark of some retinal pathologies. We investigated the effects of age, pigmentation and CX(3)CR1 deficiency on the accumulation of macrophages/activated microglia in the outer retina of young and old Cx(3)cr1(gfp/gfp) (CX(3)CR1-deficient) o...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.03.010
更新日期：2012-08-01 00:00:00
abstract：:The present study investigated if a causal relation exists between serum concentrations of precursors and metabolites of cholesterol and cognitive performance in a healthy aging population. Cognitive function addressing four domains of 144 individuals (30-80 years) was tested at baseline and after 6 years of follow-up...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00061-1
更新日期：2003-01-01 00:00:00
abstract：:Apolipoprotein E (APOE) alleles are associated with longevity in genome-wide scans, with ε4 correlated with shorter life, and ε2 with longer life, than ε3. We hypothesized that rare APOE variants with large individual effects might also contribute to long-term good health. The APOE exons and promoter were resequenced ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.09.010
更新日期：2014-03-01 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：:The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.001
更新日期：2012-08-01 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：:Decline in cognitive functions, including hippocampus-dependent spatial memory, is commonly observed at a later stage of aging (e.g., >20 months old in rodents) and typically studied after a discrete learning event. How normal aging, particularly at an early stage, affects the modulatory aspect of memory persistence i...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.02.023
更新日期：2018-07-01 00:00:00
abstract：:In a prospective study of dementia in Flanders (Belgium), we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal gene...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.04.015
更新日期：2018-09-01 00:00:00
abstract：:Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.12.027
更新日期：2013-07-01 00:00:00
abstract：:The increased life expectancy of people living with HIV-1/AIDS is accompanied by increased prevalence of HIV-1-associated neurocognitive disorder. As well, these individuals are increasingly experiencing Alzheimer's disease (AD)-like neurocognitive problems and neuropathological features such as increased deposition o...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.04.015
更新日期：2013-10-01 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：:The abnormal accumulation of amyloid fibrils in the brain is pathognomonic of Alzheimer's disease. Amyloid fibrils induce significant neuroinflammation characterized by the activation of microglia and impairment of synaptic plasticity in the brain that eventually leads to cognitive decline. Chemokine fractalkine recep...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.06.003
更新日期：2013-12-01 00:00:00
abstract：:Dopaminergic neurons in the substantia nigra produce dopamine for the nigrostriatal pathway that facilitates motor function. Postmortem examinations demonstrate an age-related loss of cells in the substantia nigra, with most of the cell loss focused on the dorsal substantia nigra compared with the ventral substantia n...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.02.006
更新日期：2012-01-01 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：:It is unknown whether lifestyle, including mental stimulation, and appropriate training interventions, may directly improve spatial navigation performance and its underlying neural substrates. Here we report that healthy younger and older men performing a cognitively demanding spatial navigation task every other day o...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2011.02.013
更新日期：2012-03-01 00:00:00
abstract：:The hippocampal perforant pathway originates in the entorhinal cortex (ERC) and terminates in the outer molecular layer of the dentate gyrus (DG). To compare the effects of normal aging and Alzheimer's disease (AD) on the elements of the perforant pathway, we compared relative perikaryal numbers (determined by countin...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90115-e
更新日期：1992-05-01 00:00:00
abstract：:The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.10.018
更新日期：2008-03-01 00:00:00
abstract：:It is widely known that the tau protein that forms the aggregates found in tauopathies like Alzheimer's disease (AD) is hyperphosphorylated. Many of the sites that are hyperphosphorylated in AD can also be found phosphorylated in non-pathological control brains, although to a lesser extend. Among the different kinases...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.04.002
更新日期：2003-12-01 00:00:00
abstract：:Alzheimer's disease of early onset versus that of late onset represent different syndromes, with distinct neuropathologies. Patients with early onset disease exhibit a more severe and more widespread loss of neurons from cortical and sub-cortical regions and the neurochemical changes involve not only the cholinergic s...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(87)90132-1
更新日期：1987-11-01 00:00:00
