A5001875012- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Genomics and Chromatin Dynamics
- Genetic Associations and Epidemiology
- Dementia and Cognitive Impairment Research
- Transcranial Magnetic Stimulation Studies
- Biological Research and Disease Studies
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Folate and B Vitamins Research
- Genomics and Rare Diseases
- MicroRNA in disease regulation
- Hereditary Neurological Disorders
- Neurological disorders and treatments
- S100 Proteins and Annexins
- Neurogenetic and Muscular Disorders Research
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
Niigata University
2016-2025
Chiba Hospital
2022
Nishi Niigata Chuo National Hospital
2022
MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such Alzheimer's disease (AD) because miRNAs relatively stable in biofluid, including serum or plasma. To determine blood miRNA AD with next-generation sequencing genome-wide, we first surveyed 45 samples. These came from 27 patients and 18 controls (discovery set) that underwent autopsy within two weeks after their sampling were neuropathologically diagnosed. We found...
Abstract Background Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer’s disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this is poorly understood because most them are located in non-coding regions, such as introns and intergenic regions. Previous reported some disease-associated affect regulatory elements including enhancers. We hypothesized AD...
Polygenic effects have been proposed to account for some disease phenotypes; these are calculated as a polygenic risk score (PRS). This is correlated with Alzheimer's (AD)-related phenotypes, such biomarker abnormalities and brain atrophy, associated conversion from mild cognitive impairment (MCI) AD. However, the AD PRS has examined mainly in Europeans, owing differences genetic structure lifestyle, it unclear whether same relationships between AD-related phenotypes exist non-European...
The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with cognitive severity Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by Braak stage, we conducted whole-genome exon array analysis an exploratory sample set consisting 213 post-mortem tissue specimens from entorinal, temporal and frontal cortices 71 brain-donor subjects: stages 0 (N=13), I-II...
Variants in the APOE gene region may explain ethnic differences association of Alzheimer’s disease (AD) with ε4. Ethnic allele frequencies for three SNPs (single nucleotide polymorphisms) were identified and tested 19,398 East Asians (EastA), including Koreans Japanese, 15,836 European ancestry (EuroA) individuals, 4985 African Americans, brain imaging measures cortical atrophy sub-samples EuroAs. Among ε4/ε4 AD risk increased substantially a dose-dependent manner number promoter SNP...
Research Article8 January 2018Open Access Source DataTransparent process Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice Kiwami Kidana Laboratory Neuropathology and Neuroscience, Graduate School Pharmaceutical Sciences, The University Tokyo, Japan Department Geriatric Medicine, Internal Komeikai Hospital, Search for more papers by this author Takuya Tatebe Kaori Ito Venture Science Laboratories, R&D Division, Daiichi-Sankyo Co. Ltd.,...
The molecular biological mechanisms of Alzheimer's disease (AD) involve disease-associated crosstalk through many genes and include a loss normal as well gain abnormal interactions among genes. A protein domain network (PDN) is collection physical bindings that occur between domains, the states PDNs in patients with AD are likely to be perturbed compared those healthy individuals. To identify PDN changes cause neurodegeneration, we analysed co-expressed each three brain regions at stage AD....
Late-onset Alzheimer's disease (LOAD), the most common form of dementia, results from complicated interactions among multiple environmental and genetic factors. Despite recent advances in analysis LOAD, more than half heritability for remains unclear. Although studies Caucasians found rare risk variants LOAD with large effect sizes, these are hardly detectable Japanese population.To identify possibly explaining part architecture people, we performed whole-exome sequencing analyses 202...
While amyloid-β lies upstream of tau pathology in Alzheimer’s disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various mutations known to facilitate aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity aggregate neurons and glial cells has remained elusive. Here, we identified genetic variations protein abundance filamin-A brains without mutations. We provided vivo biochemical...
A 47-year-old man with a family history of juvenile dementia in his mother presented memory loss and cognitive decline. Neuropsychological tests revealed impaired orientation, working memory, apraxia. Magnetic resonance imaging diffuse brain atrophy, fluorodeoxyglucose positron emission tomography (PET) showed hypometabolism the bilateral parietal lobes, posterior cingulate gyri, precuneus, suggestive Alzheimer's disease. However, amyloid-beta tau PET scans were negative. Genetic testing an...
Clinical features of cognitive performance in extreme old age differ from those pathological decline Alzheimer's disease (AD). We compared traits between 638 centenarians aged 100-115 years and 208 221 patients with AD independent facilities. The presence the apolipoprotein E (APOE) ε4 allele did not affect Mini-Mental State Examination (MMSE) scores centenarians. Centenarians retained ability to follow three consecutive commands, associated their educational background activities daily...
The AT(N) classification was proposed for categorising individuals according to biomarkers. However, profiles may vary depending on the markers chosen and target population.We stratified 177 who participated in Japanese Alzheimer's Disease Neuroimaging Initiative by cerebrospinal fluid (CSF) We compared frequency of between using total tau neurofilament light chain (NfL) as N (AT(N)tau AT(N)NfL). Baseline characteristics, longitudinal biological clinical changes were examined profiles.We...
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by mutations in CSF1R. Pathogenic exons 12-22 including coding sequence of the tyrosine kinase domain (TKD) CSF1R were previously identified. We aimed to identify patients who clinically suspected having ALSP determine pathogenicity novel variants.Sixty-one fulfilled diagnostic criteria included this study. Genetic analysis was performed for all exons. The haploinsufficiency examined frameshift RT-PCR....
Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of circuit rewiring various neurodevelopmental disorders human cognition. We previously showed that Otx2 homeoprotein, essential for formation, is recaptured during postnatal maturation parvalbumin-positive interneurons (PV cells) to activate period mouse visual cortex. Cortical only interneuron-enriched transcription factor known...
Abstract Amyloid-β (Aβ) accumulation in the brain triggers pathogenic cascade for Alzheimer’s disease (AD) development. The secretory protein FAM3C (also named ILEI) is a candidate an endogenous suppressor of Aβ production. In this study, we found that expression was transcriptionally downregulated AD brain. To determine transcriptional mechanism human gene, delineated minimal 5′-flanking sequence required basal promoter activity. From database search DNA-binding motifs, analysis using...
Abstract In amyotrophic lateral sclerosis (ALS), TAR DNA-binding protein 43 (TDP-43), which is encoded by TARDBP , forms aggregates in the motor cortex. This aggregate formation may be triggered an increase TDP-43 level with aging. However, amount of autoregulated alternative splicing 3′UTR, and how this autoregulation affected aging remains to elucidated. We found that DNA demethylation autoregulatory region 3′UTR reduced increased mRNA expression. Furthermore, human cortex, we was...
Abstract INTRODUCTION The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse. METHODS Logistic regression identified AD‐associated haplotypes East Asian ( N = 5249) and European 8588) populations. Association analysis between traits or plasma biomarkers was conducted. of non‐synonymous mutations were assessed cell‐based systems. RESULTS Protective variants/haplotypes the Haplotype Hap_A showed a...
Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), activator eIF2. VWM occurs with mutation the genes encoding eIF2B subunits (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5). However, little known regarding underlying pathogenetic mechanisms or how to treat patients VWM. Here we describe identification detailed analysis a new spontaneous mutant mouse harboring point...
The aberrant metabolism of amyloid β peptide (Aβ) has been implicated in the etiology Alzheimer disease (AD). Aβ is produced via sequential cleavage precursor protein (APP) by β- and γ-secretases. However, precise regulatory mechanism generation still remains unclear. To gain a better understanding molecular production, we established genetic screening method based on CRISPR/Cas9 system to identify novel regulators production. We successfully identified calcium integrin-binding 1 (CIB1) as...
Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related association with clinical and imaging features.Mutational analysis CSF1R was performed for 100 consecutive patients leukoencephalopathy. Sequence copy number variation (CNV) analyses were performed. genomic ranges deletions determined long-read sequencing. Ligand-dependent autophosphorylation...