A5101733003- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Prion Diseases and Protein Misfolding
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Functional Brain Connectivity Studies
- Pituitary Gland Disorders and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Adrenal and Paraganglionic Tumors
- S100 Proteins and Annexins
- Advanced Neuroimaging Techniques and Applications
- Sperm and Testicular Function
- Neuroblastoma Research and Treatments
- Down syndrome and intellectual disability research
- Sarcoma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Health, Environment, Cognitive Aging
- Bioinformatics and Genomic Networks
- Lymphoma Diagnosis and Treatment
- Tryptophan and brain disorders
- Neuroendocrine Tumor Research Advances
Osaka City University
2015-2024
Kanazawa University Hospital
2018-2024
Nikon (Japan)
2022-2024
Kanazawa University
2018-2024
Osaka Metropolitan University
2022-2023
Shukutoku University
2023
Alzheimer’s Disease Neuroimaging Initiative
2023
Shinshu University Hospital
2023
Kyowa Chemical Industry (Japan)
2023
J-Power (Japan)
2023
The amyloid beta-protein (A beta) that is progressively deposited in Alzheimer's disease (AD) arises from proteolysis of the integral membrane protein, beta-amyloid precursor protein (beta APP). Although A beta formation appears to play a seminal role AD, only few studies have examined chemical structure purified brain, and there are discrepancies among findings. We describe new method for rapid extraction purification minimizes artifactual proteolysis. by two-dimensional reverse-phase HPLC...
Soluble oligomers of amyloid beta (Abeta), rather than fibrils, have been proposed to initiate synaptic and cognitive dysfunction in Alzheimer's disease (AD). However, there is no direct evidence humans that this mechanism can cause AD. Here, we report a novel precursor protein (APP) mutation may provide address question.A Japanese pedigree showing Alzheimer's-type dementia was examined for mutations APP, PSEN1, PSEN2. In addition, 5,310 people, including 2,121 patients with AD, were...
Although amyloid β (Aβ) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing E693Δ mutation, which causes by enhanced Aβ oligomerization without fibrillization. The displayed age-dependent accumulation intraneuronal from 8 months but no extracellular deposits even at 24 months. Hippocampal plasticity memory were...
Leydig cells are thought to be the source of most, if not all, testosterone produced by testis. The goal this study was obtain quantitative information about rat and their organelles that might correlated with pertinent physiological biochemical data available either now or in future. Morphometric analysis mature normal rats carried out on tissue fixed perfusion buffered glutaraldehyde, embedded glycol methacrylate for light microscopy Epon electron microscopy. In a whole testis, 82.4%...
Abstract Intraneuronal accumulation of amyloid β (Aβ) is an early pathological change in Alzheimer's disease. Previously, we showed that the E693Δ mutation (referred to as “Osaka” mutation) precursor protein (APP) caused intracellular Aβ oligomers and apoptosis transfected COS‐7 cells. We also transgenic mice expressing APP (APP OSK ) displayed both age‐dependent intraneuronal from 8 months age apparent neuronal loss hippocampus at 24 age. These findings indicate cause cell death, but...
Abstract Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation amyloid-β (Aβ) peptide into plaques and microtubule protein tau neurofibrillary tangles (NFTs)—are hallmarks disease. However, other brain processes are thought to be key mediators Aβ plaque NFT pathology. How these additional pathologies evolve over course is currently unknown. Here we show that proteomic measurements in autosomal dominant AD...
We provide the first evidence for capability of a high-resolution positron emission tomographic (PET) imaging system in quantitatively mapping amyloid accumulation living precursor protein transgenic (Tg) mice. After intravenous administration N -[ 11 C]methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (or [ C]PIB “Pittsburgh Compound-B”) with high-specific radioactivity, Tg mice exhibited high-level retention radioactivity amyloid-rich regions. PET investigation over an extended range...
<h3>Background</h3> Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid β-peptide (Aβ)–centric theory holds that Aβ is involved in pathogenesis of sporadic AD. Mutations precursor protein (<i>APP</i>), presenilin 1 (<i>PSEN1</i>), and 2 (<i>PSEN2</i>) genes lead to increased levels before symptoms arise. <h3>Objectives</h3> To evaluate pattern Pittsburgh Compound B (PiB) retention subjects with different autosomal dominant mutations...
The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations the gene. Hyperphosphorylation of considered crucial age-related formation neurofibrillary tangles (NFTs) correlating well neurotoxicity and cognitive defects. Transgenic mice expressing FTD mutant tau-P301L recapitulate human pathology progressive neuronal impairment accumulation NFT. Here, we studied for parameters...
Core pathologies of Alzheimer's disease (AD) are aggregated amyloid-β peptides (Aβ) and tau, the latter is also characteristic diverse neurodegenerative tauopathies. These amyloid lesions provoke microglial activation, recent neuroimaging technologies have enabled visualization this response in living brains using radioligands for peripheral benzodiazepine receptor known as 18 kDa translocator protein (TSPO). Here, we elucidated contributions Aβ tau deposits to vivo TSPO signals pursuit...
Amyloid-β, tau, and α-synuclein, or more specifically their soluble oligomers, are the aetiologic molecules in Alzheimer's disease, tauopathies, α-synucleinopathies, respectively. These proteins have been shown to interact accelerate each other's pathology. Clinical studies of amyloid-β-targeting therapies disease revealed that treatments after onset little benefit on patient cognition. findings prompted us explore a preventive medicine which is orally available, has few adverse effects,...
Abstract Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer’s disease, but the functional brain mechanisms that support remain elusive. Given previous findings normal ageing, we tested hypothesis higher segregation brain’s connectome into distinct networks represents a mechanism underlying disease. Using resting-state MRI, assessed both MRI global system segregation, i.e. balance between-network to within-network connectivity, and alternate index...
"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted has been well established in symptomatic Alzheimer disease (AD), but is underexplored preclinical AD. Prior studies have typically used structural MRI, resting-state functional connectivity (FC) remains underexplored. Our model predicted from FC 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained 145 amyloid-negative, 151 AD, and 156...
Abstract Background Glial fibrillary acidic protein (GFAP) is a promising candidate blood‐based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease‐associated changes, clinical correlates, biofluid‐type dependency will influence utility. Methods We evaluated plasma, serum, cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage disease. Results...
The SOMAscan assay has an advantage over immunoassay-based methods because it measures a large number of proteins in cost-effective manner. However, the performance this technology compared to routinely used immunoassay techniques needs be evaluated. We performed comparative analyses and protein measurements for five cerebrospinal fluid (CSF) associated with Alzheimer's disease (AD) neurodegeneration: NfL, Neurogranin, sTREM2, VILIP-1, SNAP-25. biomarkers measured ADNI (N = 689), Knight-ADRC...