Publications by authors named "Hiroyasu Akatsu"

Article Synopsis
  • Scientists don't fully understand what causes Alzheimer's disease (AD), but they know some genes are involved.
  • Researchers found a link between two genes, CELF1 and KLC1, showing that low levels of CELF1 are common in Alzheimer's brains and affect another gene's activity.
  • When CELF1 is less active, it leads to an increase in a harmful version of the KLC1 gene, which may contribute to the development of Alzheimer's disease.
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Introduction: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI).

Methods: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months.

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Background: Polygenic effects have been proposed to account for some disease phenotypes; these effects are calculated as a polygenic risk score (PRS). This score is correlated with Alzheimer's disease (AD)-related phenotypes, such as biomarker abnormalities and brain atrophy, and is associated with conversion from mild cognitive impairment (MCI) to AD. However, the AD PRS has been examined mainly in Europeans, and owing to differences in genetic structure and lifestyle, it is unclear whether the same relationships between the PRS and AD-related phenotypes exist in non-European populations.

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Article Synopsis
  • The study investigates lipid abnormalities in bipolar disorder (BD) by analyzing the expression levels of certain enzyme proteins in patients' brains, particularly those believed to be affected by mood stabilizers like lithium.
  • The research measured the expression of several proteins in the prefrontal cortex, finding that PTEN levels were significantly lower, while Akt1 and GSK3β levels were higher in BD patients compared to controls.
  • The results indicate that the expression of key proteins involved in mood regulation is significantly altered in BD, with lithium-treated patients showing distinct differences from those not receiving treatment.
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Aims: Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021).

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Background: It is important to investigate neural as well as muscle morphological adaptations to evaluate the effects of exercise training on older adults.

Aims: This study was aimed to investigate the effects of home-based bodyweight squat training on neuromuscular adaptation in older adults.

Methods: Twenty-five community-dwelling older adults (77.

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Background: As Japan undergoes population aging, nursing care workers play an important role in supporting older adults in the community, which has been particularly critical during COVID-19 pandemic. However, the knowledge, attitudes, and practices (KAP) among nursing care workers regarding COVID-19 have not been fully elucidated.

Methods: A self-administered questionnaire survey was conducted in June 2020 among 481 nursing care workers in the nursing care facilities in Aichi, Japan.

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Iron is an essential nutrient in the body. However, iron generates oxidative stress and hence needs to be bound to carrier proteins such as the glycoprotein transferrin (Tf) in body fluids. We previously reported that cerebrospinal fluid contains Tf glycan-isoforms that are derived from the brain, but their origins at the cellular level in the brain have not yet been elucidated.

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The pathological changes of Alzheimer's disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system.

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Limb-loaded walking using ankle weights has been widely applied to increase exercise intensity in older adults. Examining changes in the activation pattern between proximal (RFP) and distal (RFD) regions of the rectus femoris (RF) muscle is key to clarifying gait deficits in older adults. The aim of this study was to determine regional neuromuscular regulation within the RF muscle following three-month limb-loaded walking in older adults.

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Since the start of the COVID-19 pandemic, many healthy older adults have been less willing to engage in group exercise for fear of contracting this illness. Therefore, there is a need for an effective home-based exercise program to prevent frailty in the elderly. In this study, we assessed the effectiveness of ankle weights as a frailty prevention device for older adults.

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Intracellular accumulation of abnormal proteins with conformational changes is the defining neuropathological feature of neurodegenerative diseases. The pathogenic proteins that accumulate in patients' brains adopt an amyloid-like fibrous structure and exhibit various ultrastructural features. The biochemical analysis of pathogenic proteins in sarkosyl-insoluble fractions extracted from patients' brains also shows disease-specific features.

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An efficient analytical platform is required to characterize the human metabolome in pathology. For this purpose, ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) combined with chemical derivatization stands out as one of the most powerful techniques. A targeted metabolomics platform for 11 bile acids (BAs) profiling in human serum and bile samples using a stable isotope labeling derivatization (SILD) was applied.

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Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer's disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry.

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Tauopathies are neurodegenerative diseases that are characterized by pathological accumulation of tau protein. Tau is hyperphosphorylated in the brain of tauopathy patients, and this phosphorylation is proposed to play a role in disease development. However, it has been unclear whether phosphorylation is different among different tauopathies.

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Alpha-synuclein (α-Syn), a neuronal protein, has been linked to the inflammation and development of neurodegenerative diseases. In a number of neurodegenerations, α-Syn has been investigated in the central nervous system and cerebrospinal fluid. However, there are few studies concerning the variations in peripheral α-Syn in postmortem Alzheimer's disease (AD) pathology.

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Article Synopsis
  • The study focuses on the characteristics of amyloid β (Aβ) oligomers, which are toxic species involved in Alzheimer's disease (AD) but are difficult to analyze due to their instability.
  • Researchers developed a modified version of Aβ42 (SS-Aβ42) that forms stable oligomers and proved to be more cytotoxic in cell cultures than its wild-type counterpart and a more aggregative mutant.
  • An antibody, TxCo-1, was created to specifically target the toxic form of SS-Aβ42, and its use revealed that this oligomeric form is associated with brain structures in Alzheimer’s patients, providing insights into its role in AD pathology.
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Multiple gene mutations cause familial frontotemporal lobar degeneration (FTLD) while no single gene mutations exists in sporadic FTLD. Various proteins aggregate in variable regions of the brain, leading to multiple pathological and clinical prototypes. The heterogeneity of FTLD could be one of the reasons preventing development of disease-modifying therapy.

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Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown.

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The early-stage pathologies of frontotemporal lobal degeneration (FTLD) remain largely unknown. In VCP-KI mice carrying VCP gene mutation linked to FTLD, insufficient DNA damage repair in neural stem/progenitor cells (NSCs) activated DNA-PK and CDK1 that disabled MCM3 essential for the G1/S cell cycle transition. Abnormal neural exit produced neurons carrying over unrepaired DNA damage and induced early-stage transcriptional repression-induced atypical cell death (TRIAD) necrosis accompanied by the specific markers pSer46-MARCKS and YAP.

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Background: Emerging evidence indicates that the misfolded tau protein can propagate aggregates between cells in a prion-like manner. This prion activity has been typically studied in brain extracts of patients with Alzheimer's disease (AD), but not in the olfactory region that can be a potential biomarker in AD.

Objective: To investigate the prion seeding activity of tau in nasal mucosa tissues using a cell culture model of tau propagation.

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