Abstract：
:We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD). We detected 1 patient harboring a homozygous SNCA p.A53V substitution albeit with an autosomal dominant pattern of disease inheritance (frequency 2/860 = 0.2%). The proband manifested slow and progressive parkinsonism at 55 years. Later she complicated with cognitive decline and hallucinations. Several of her immediate family members also presented with parkinsonism, cognitive decline, and psychosis. Positron emission tomography imaging of 18F-6-fluoro-L-dopa (18F-DOPA) uptake, 11C(+)dihydrotetrabenzine (type 2 vesicular monoamine transporter), and 11C-d-threo-methylphenidate (a plasmalemmal dopamine transporter marker) binding in the striatum were significantly reduced. Hence, alpha-synuclein p.A53V homozygous mutation leads to a distinct phenotype of progressive parkinsonism and cognitive decline, commonly observed in patients with SNCA missense mutation or multiplications.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Yoshino H,Hirano M,Stoessl AJ,Imamichi Y,Ikeda A,Li Y,Funayama M,Yamada I,Nakamura Y,Sossi V,Farrer MJ,Nishioka K,Hattori Ndoi
10.1016/j.neurobiolaging.2017.05.022subject
Has Abstractpub_date
2017-09-01 00:00:00pages
248.e7-248.e12eissn
0197-4580issn
1558-1497pii
S0197-4580(17)30189-6journal_volume
57pub_type
杂志文章abstract：:Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most likely linked to an impairment of insulin signaling in the brain. Liraglutide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin signaling and shows neuroprotective properties. In the present study, we analyzed t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.04.009
更新日期：2013-02-01 00:00:00
abstract：:To better understand the role of insulin signaling in the development of Alzheimer's disease (AD), we utilized an animal model (intracerebroventricular injection of streptozotocin-ic-streptozotocin (STZ)) that displays insulin resistance only in the brain and exhibits AD pathology. In this model, deficits in hippocamp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.12.002
更新日期：2012-02-01 00:00:00
abstract：:Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample con...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.02.014
更新日期：2019-06-01 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：:Cortisol and ACTH exhibit circadian rhythmicity, peaking in the early morning. These peaks are associated with increased activity and alertness. We sought to determine whether self-reported daily rhythms predict outcome of a.m. and p.m. CRH challenge in elderly subjects. We surveyed 96 elderly subjects to determine da...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90029-b
更新日期：1993-01-01 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：:Using resting state (RS) functional magnetic resonance imaging (fMRI), the connectivity patterns of the default mode (DMN), frontoparietal, executive, and salience networks were explored in 13 Alzheimer's disease (AD) patients, 12 amnestic mild cognitive impairment (aMCI) patients, and 13 healthy controls. Compared wi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.007
更新日期：2012-08-01 00:00:00
abstract：:The sporadic form of Alzheimer disease, late onset Alzheimer's disease (LOAD), is a multifactorial disease; a strong link between nutritional and genetic factors with normal aging and dementia is supported by studies on nutrition, metabolism, and neurodegeneration. Specifically, the involvement of homocysteine (HCY) a...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/j.neurobiolaging.2011.01.012
更新日期：2011-07-01 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：:Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and su...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.08.005
更新日期：2014-02-01 00:00:00
abstract：:This study investigates the age associated changes in hemorheological properties and cerebral blood flow. Partial correlations indicate that part of the age-dependent decrease in flow velocities can be attributed to a hemorheological decrement resulting in part from enhanced oxidative stress in the aged. A possible li...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/s0197-4580(00)00118-4
更新日期：2000-03-01 00:00:00
abstract：:A variety of studies have shown an effect of estrogen on dopamine function and suggest that estrogen may modulate central dopaminergic activity. Positron emission tomography (PET) and the dopamine metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate dopaminergic function in the frontal cortex and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00323-2
更新日期：2002-05-01 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：:Dementia is believed to result from the loss of selective neurons within the brain, but approaches for systematic study of that degenerative process are hampered by the complexity of the neuronal milieu. Tissue culture models provide a means to reduce dramatically the variables inherent in the study of neuronal plasti...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(88)80142-8
更新日期：1988-09-01 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 impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.12.019
更新日期：2016-04-01 00:00:00
abstract：:The midsagittal cross-sectional dimensions of the corpus callosum, the coronal cross-sectional area of the lateral ventricles at the level of the pons, and a three-dimensional estimate of intracranial volume were derived from magnetic resonance brain images obtained from 45 monozygotic and 40 dizygotic male twin pairs...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/s0197-4580(00)00086-5
更新日期：2000-01-01 00:00:00
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 seque...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.06.036
更新日期：2018-12-01 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：:During aging, lifestyle-related factors shape the brain's response to insults and modulate the progression of neurodegenerative pathologies such as Alzheimer's disease (AD). This is the case for chronic hyperglycemia associated with type 2 diabetes, which reduces the brain's ability to handle the neurodegenerative bur...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.04.003
更新日期：2020-08-01 00:00:00
abstract：:The development of amyloid imaging compounds has allowed in vivo imaging of amyloid deposition. In this study, we examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB) positron emission tomography data from the Baltimore Longitudinal Study of Aging. We used...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.05.030
更新日期：2013-12-01 00:00:00
abstract：:N-Methyl-D-Aspartate (NMDA) receptors are believed to play a critical role in excitotoxic cell death in the CNS. The distribution of NMDA-preferring binding sites is compared here with the patterns of selective neuronal death observed in Alzheimer's disease and following transient ischemia. The distribution of NMDA re...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90148-6
更新日期：1989-09-01 00:00:00
abstract：:Decreases in the activity or density of dopamine D2 receptor (D2R) have been associated with age-related changes and neurodegenerative diseases such as Parkinson's disease. There are two isoforms of the D2R, termed the D2 long receptor (D2LR) and D2 short receptor (D2SR). To study the function of these two isoforms an...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.04.005
更新日期：2005-04-01 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
abstract：:The release of endogenous and newly synthesized acetylcholine (ACh) was examined in neostriatal slices prepared from young adult (10-month) and aged (28-month) Fischer 344 rats. Both spontaneous and potassium-stimulated release were tested after various in vitro incubation times (1, 3 or 5 hr). The potassium-stimulate...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90006-l
更新日期：1990-07-01 00:00:00
abstract：:This paper describes regional brain energy metabolism, sensorimotor, and memory functions in mature (12 months) and old (24 months) C57BL/6 mice. Male mice were tested across a variety of sensorimotor procedures and in the Morris water maze before evaluating brain uptake of fluorodeoxyglucose (FDG) in the resting stat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00099-3
更新日期：2000-09-01 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：:While aged monkeys of several species show cerebral amyloid deposition in senile plaques and blood vessels similar to that seen in human aging and Alzheimer's disease (AD), studies of great apes have been limited. Using histological and immunohistochemical methods, we examined the brains of four orangutans aged 10, 28...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00012-2
更新日期：1997-03-01 00:00:00
abstract：:Carboxyl-terminal fragments of beta amyloid precursor protein (betaAPP) were expressed in mice under the transcriptional control of an ubiquitous promoter system, based upon a chicken beta-actin (betaA) promoter combined with cytomegalovirus (CMV) enhancer to obtain a systemic overproduction of amyloid beta protein (A...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00043-8
更新日期：1998-01-01 00:00:00
abstract：:The present study was designed to examine the effects of the aging process on the response of motoneurons to axotomy. Accordingly, in aged cats using intracellular recording techniques, the electrophysiological properties of axotomized lumbar spinal cord motoneurons were compared with those of control (nonaxotomized) ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90035-v
更新日期：1992-03-01 00:00:00
