A5101570428- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- CCD and CMOS Imaging Sensors
- Analog and Mixed-Signal Circuit Design
- Parkinson's Disease Mechanisms and Treatments
- Neural Networks and Applications
- Coronary Interventions and Diagnostics
- Genetic Neurodegenerative Diseases
- Cardiac Imaging and Diagnostics
- Advanced Memory and Neural Computing
- Neuroscience and Neural Engineering
- Lipoproteins and Cardiovascular Health
- Advancements in PLL and VCO Technologies
- Semiconductor Lasers and Optical Devices
- Cerebrovascular and Carotid Artery Diseases
- Mitochondrial Function and Pathology
- Photonic and Optical Devices
- Neurological disorders and treatments
- Network Traffic and Congestion Control
- Particle Detector Development and Performance
- Neurological Disease Mechanisms and Treatments
- Software-Defined Networks and 5G
- Interconnection Networks and Systems
- Advanced Optical Network Technologies
- Low-power high-performance VLSI design
Tokyo Metropolitan Institute of Gerontology
2021-2025
Wakayama Medical University
2024-2025
The University of Tokyo
2015-2024
Tokyo Metropolitan Geriatric Hospital
2020-2024
University of California, San Francisco
2024
San Francisco VA Medical Center
2024
Fukuoka University
2013-2023
University of Tokyo Hospital
1998-2023
Neurology, Inc
2022-2023
Chiba University
2023
CNS neurons are endowed with the ability to recover from cytotoxic insults associated accumulation of proteinaceous polyglutamine aggregates via a process that appears involve capture and degradation by autophagy. The ubiquitin-proteasome system protects cells against proteotoxicity degrading soluble monomeric misfolded aggregation-prone proteins but is ineffective against, impaired by, non-native protein oligomers. Here we show autophagy induced in response ubiquitin proteasome activity. We...
Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system widely considered be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement genetic components.
Background Alpha-synuclein (SNCA) gene expression is an important factor in the pathogenesis of Parkinson's disease (PD). Gene multiplication can cause inherited PD, and promoter polymorphisms that increase SNCA are associated with sporadic PD. CpG methylation region may also influence expression. Methodology/Principal Findings By using cultured cells, we identified a island which status altered along increased Postmortem brain analysis revealed regional non-specific differences this...
Abstract Background Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials early stage Alzheimer’s disease (AD). In this study, we elucidate utility combination plasma amyloid-β (Aβ)-related tau phosphorylated at threonine 217 (p-tau217) predict abnormal Aβ-positron emission tomography (PET) preclinical prodromal AD. Methods We designed cross-sectional...
CNS neurons are endowed with the ability to recover from cytotoxic insults associated accumulation of proteinaceous aggregates in mouse models polyglutamine disease, but cellular mechanism underlying this phenomenon is unknown. Here, we show that autophagy essential for elimination aggregated forms mutant huntingtin and ataxin-1 cytoplasmic not nuclear compartments. Human orthologs yeast genes, molecular determinants autophagic vacuole formation, recruited inclusion bodies vitro vivo . These...
By a quantitative Western immunoblot analysis, the intracellular levels of two principal sigma subunits, 70 (sigma D, rpoD gene product) and 38 S, rpoS product), minor 54 N, rpoN 28 F, rpoF were determined in Escherichia coli strains, W3110 MC4100. The results indicated that are maintained at 10 50%, respectively, level both strains growing exponential stationary phases, but agreement with previous measurement for strain MC4100 (M. Jishage A. Ishihama, J. Bacteriol. 177:6832-6835, 1995), was...
<h3>Background</h3> Increased frequency of pathogenic variants in<i>GBA</i>, the causative gene for Gaucher disease, has been suggested to be associated with Parkinson disease (PD). <h3>Objectives</h3> To conduct comprehensive resequencing of<i>GBA</i>to identify all sequence and investigate association these PD. <h3>Design</h3> Case-control study. <h3>Setting</h3> Multicenter university-based <h3>Participants</h3> Five hundred thirty-four patients PD, 34 families in which multiple PD are...
The hallmark of Alzheimer's disease (AD) pathology is an accumulation amyloid β (Aβ) and phosphorylated tau, which are encoded by the precursor protein (APP) microtubule-associated tau (MAPT) genes, respectively. Less than 5% all AD cases familial in nature, i.e. caused mutations APP, PSEN1 or PSEN2. Almost found them related to overproduction Aβ1-42, prone aggregation. While these genes mutation free, their function, those could be compromised sporadic as well. In this study, pyrosequencing...
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal-dominant neurodegenerative disorder characterized by widespread fasciculations, proximal-predominant muscle weakness, atrophy followed distal involvement. To date, large families affected HMSN-P have been reported from two different regions in Japan. Linkage haplotype analyses of previously new the use high-density SNP arrays further defined minimum candidate region 3.3 Mb chromosomal 3q12....
Abstract Introduction We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J‐ADNI) and compared the basic characteristics progression profiles with those of ADNI in North America. Methods A total 537 subjects normal cognition, late amnestic mild cognitive impairment (LMCI), or disease (AD) were enrolled using same criteria as ADNI. Rates changes representative functional measures for amyloid positron emission tomography‐ cerebrospinal fluid β(1–42)‐positive LMCI AD between...
Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson (PD) and dementia Lewy bodies (DLB). To investigate the role of GBA in multiple system atrophy (MSA), we analyzed a large case-control series.We sequenced coding regions flanking splice sites 969 MSA patients (574 Japanese, 223 European, 172 North American) 1509 control subjects (900 315 294 American). We focused solely on Gaucher-disease-causing variants.In Japanese series, found nine carriers...
Abstract The timing and characteristics of neuronal death in Alzheimer’s disease (AD) remain largely unknown. Here we examine AD mouse models with an original marker, myristoylated alanine-rich C-kinase substrate phosphorylated at serine 46 (pSer46-MARCKS), reveal increase necrosis during pre-symptomatic phase a subsequent decrease symptomatic phase. Postmortem brains mild cognitive impairment (MCI) rather than patients remarkable necrosis. In vivo imaging reveals instability endoplasmic...
Significance To extract critical information from Alzheimer’s disease (AD) postmortem brains that may otherwise be lost, we chose to screen epigenetic signatures. Epigenome analysis is a robust methodology in terms of its cell type and gene specificity, suitability for high-throughput analysis, resistance degradation. Analysis the neuron-specific methylome revealed variety differentially methylated genes, including BRCA1 . We demonstrate pathogenic relevance compromised genomic integrity by...
Gait movies recorded in daily clinical practice are usually not filmed with specific devices, which prevents neurologists benefitting from leveraging gait analysis technologies. Here we propose a novel unsupervised approach to quantifying features and extract cadence normal parkinsonian home video camera by applying OpenPose, deep learning-based 2D-pose estimator that can obtain joint coordinates pictures or videos monocular camera.Our proposed method consisted of two distinct phases:...
Facial nerve palsy (or Bell's palsy) has occasionally been reported following the administration of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2 and mRNA-1273). Our study investigated such cases using a large self-reporting database from USA (Vaccine Adverse Event Reporting System [VAERS]).A disproportionality analysis, adjusted for age sex, was conducted VAERS reports individuals who were vaccinated at 18 years or over, between January 2010 April 2021.The analysis revealed...
Abstract Recent studies suggest that increased cerebrospinal fluid (CSF) phospho-tau is associated with brain amyloid pathology rather than the tau pathology. However, confirmation using gold standard neuropathological assessments remains limited. This study aimed to determine background pathologies aberrant CSF p-tau181 and amyloid-beta 1–42 (Aβ42) in Alzheimer’s disease (AD) other neurodegenerative diseases. We retrospectively studied all patients antemortem postmortem neuropathologic data...
Accumulation of insoluble alpha-synuclein aggregates in the brain is characteristic Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Although numerous studies on aggregation properties have been reported, little known about its degradation so far. In view proteolytic degradation, we found that serine protease neurosin (kallikrein-6) degrades co-localizes pathological inclusions such as glial cytoplasmic inclusions. vitro study showed prevented polymerization by...