A Retrospective Cohort Study of a Newly Proposed Criteria for Sporadic Creutzfeldt-Jakob Disease.

Background/objectives: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD.

Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of β-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APP) in the neurons.

Enhancing Long-Term Durability of Electrochemical Reactors Producing Formate from CO and Water Designed for Integration with Solar Cells.

Artificial photosynthetic cells producing organic matter from CO and water have been extensively studied for carbon neutrality, and the research trend is currently transitioning from proof of concept using small-sized cells to large-scale demonstrations for practical applications. We previously demonstrated a 1 m size cell in which an electrochemical (EC) reactor featuring a ruthenium (Ru)-complex polymer (RuCP) cathode catalyst was integrated with photovoltaic cells. In this study, we tackled the remaining issue to improve the long-term durability of cathode electrodes used in the EC reactors, demonstrating high Faradaic efficiencies exceeding 80% and around 60% electricity-to-chemical energy-conversion efficiencies of a 75 cm sized EC reactor after continuous operation for 3000 h under practical conditions.

Autochthonous Cryptococcus gattii genotype VGIIb infection in a Japanese patient with anti-granulocyte-macrophage colony-stimulating factor antibodies.

A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens.

Sporadic Late-onset Nemaline Myopathy Associated with Sjögren's Syndrome.

We report the case of a 46-year-old female patient who developed a subacute progression of axial and proximal muscle weakness. Laboratory findings revealed mildly elevated serum creatine kinase levels. No monoclonal gammopathy was detected.

Nationwide Laboratory Surveillance of Progressive Multifocal Leukoencephalopathy in Japan: Fiscal Years 2011-2020.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis.

Vacuoles related to tissue neuron-astrocyte ratio and infiltration of macrophages/monocytes contribute to hyperintense brain signals on diffusion-weighted magnetic resonance imaging in sporadic Creutzfeldt-Jakob disease.

Background: Radiological features in patients with sporadic Creutzfeldt-Jakob disease (sCJD) are hyperintensity of the cerebral cortex and the basal ganglia displayed by diffusion-weighted magnetic resonance imaging (DW-MRI). We performed a quantitative study on neuropathological and radiological findings.

Methods: Patient 1 received a definite diagnosis of MM1-type sCJD, while patient 2 received a definite diagnosis of MM1 + 2-type sCJD.

Cerebrospinal Fluid Biomarkers and Amyloid-β Elimination from the Brain in Cerebral Amyloid Angiopathy-Related Inflammation.

Background: Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results.

Objective: We investigated the relationship between CSF amyloid-β protein (Aβ) and vascular pathological findings to elucidate the mechanisms of Aβ elimination from the brain in CAA-ri.

Methods: We examined Aβ40 and Aβ42 levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer's disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study.

Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial.

Background: Previous in vitro and in vivo studies on Alzheimer's disease (AD) models have reported that rosmarinic acid (RA) can inhibit the formation of amyloid-β fibrils as well as the oligomerization and deposition of amyloid-β protein. Melissa officinalis (M. officinalis) extract containing 500 mg of RA is tolerable and safe in healthy individuals and patients with mild AD dementia.

A case of autoimmune glial fibrillary acidic protein astrocytopathy presenting with magnetic resonance imaging mimics of multiple sclerosis.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory disorder of the central nervous system. On magnetic resonance imaging, the neuroradiological signature is a linear radial enhancement pattern of cerebral white matter (MRI). Dawson's fingers, on the other hand, and ovoid lesions with open-ring enhancement have long been recognized as distinct features of multiple sclerosis (MS).

Specific electroencephalogram features in the very early phases of sporadic Creutzfeldt-Jakob disease.

Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges.

Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases.

Background: No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset.

Methods: We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases.

Deterioration after Liver Transplantation and Transthyretin Stabilizer Administration in a Patient with ATTRv Amyloidosis with a Leu58Arg (p.Leu78Arg) TTR Variant.

We herein report a 44-year-old Japanese man with hereditary transthyretin amyloidosis (ATTRv amyloidosis) harboring the variant Leu58Arg (p.Leu78Arg) in TTR in whom we conducted an observational study with liver transplantation (LT) and transthyretin (TTR) stabilizers (tafamidis and diflunisal) for 9 years. This patient showed gradual deterioration of sensory, motor, and autonomic neuropathy symptoms after LT.

Transmission of Cerebral β-Amyloidosis Among Individuals.

Deposition of amyloid β protein (Aβ) in the brain (cerebral β-amyloidosis) is a hallmark of Alzheimer's disease (AD). So far, there have been increasing number of experimental studies using AD mouse model that cerebral β-amyloidosis could be transmitted among individuals as prion-like mechanism. Furthermore, several pathological studies using autopsied patients with iatrogenic Creutzfeldt-Jakob disease (CJD) showed that cerebral β-amyloidosis in addition to the CJD pathology could be transmitted among humans via medical procedures, such as human growth hormone derived from cadaver injection and cadaveric dura mater graft.

Exogenous Aβ seeds induce Aβ depositions in the blood vessels rather than the brain parenchyma, independently of Aβ strain-specific information.

Little is known about the effects of parenchymal or vascular amyloid β peptide (Aβ) deposition in the brain. We hypothesized that Aβ strain-specific information defines whether Aβ deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aβ plaques and cerebral amyloid angiopathy (CAA), and performed a seeding study using an Alzheimer's disease (AD) mouse model in which brain homogenates derived from the autopsied patients were injected intracerebrally.

Rosmarinic acid suppresses tau phosphorylation and cognitive decline by downregulating the JNK signaling pathway.

Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer's disease (AD) as it potently suppresses the aggregation of amyloid β (Aβ); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear. The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Aβ and phosphorylated tau accumulation, and improved cognitive function in the 3 × Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation.

A new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment and dementia around 5 min.

This study aimed to develop a new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment (MCI) and dementia. We performed C-ABC in subjects with dementia (n = 422), MCI (n = 145), and normal cognition (NC; n = 574), and analyzed by age stratum (50s, 60s, and 70-85 years). To distinguish MCI from NC, the C-ABC total combined score, which were calculated by dividing the C-ABC total score by the C-ABC required time, revealed the best area under the curves (AUC) at 0.

Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy-related inflammation.

Objectives: To clarify pathomechanisms of cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri).

Methods: We collected cerebrospinal fluid (CSF) samples of nine patients with CAA-ri of before (acute CAA-ri group) and after treatment (post-treatment CAA-ri group) and nine patients with CAA (CAA without inflammation group). We examined anti-amyloid β protein (Aβ) antibody titer by ELISA, and measured 27 Cytokines, nine matrix metalloproteinases (MMPs), and four tissue inhibitors of MMPs (TIMPs) by multiplexed fluorescent bead-based immunoassay.

Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer's disease progression.

We conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer's disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M.

MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type.

Objective: To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity.

Methods: We reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases.

Results: According to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death.

Diffusion-weighted magnetic resonance imaging in dura mater graft-associated Creutzfeldt-Jakob disease.

Purpose: To elucidate the extension patterns of the hyperintense areas on diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD).

Methods: We collected the DW-MRI of dCJD cases identified by the CJD Surveillance Committee in Japan, between April 1999 and February 2018. The dCJD cases were classified into non-plaque and plaque-types.

Focal sharp waves are a specific early-stage marker of the MM2-cortical form of sporadic Creutzfeldt-Jakob disease.

Periodic sharp wave complexes (PSWCs), identified using electroencephalography, are observed in less than half of patients with the methionine homozygosity type 2 cortical (MM2c) form of sporadic Creutzfeldt-Jakob disease (sCJD), and only at a later stage of the disease. In this study, we identified early and specific markers on the electroencephalograms (EEGs) of patients with MM2c-sCJD. We retrospectively investigated the clinical records, EEGs, and magnetic resonance imaging (MRI) scans of patients diagnosed with sCJD and compared the EEG findings of MM2c-sCJD and MM1/classic sCJD groups.

Characterization of Sporadic Creutzfeldt-Jakob Disease and History of Neurosurgery to Identify Potential Iatrogenic Cases.

We previously reported a phenotype of Creutzfeldt-Jakob disease (CJD), CJD-MMiK, that could help identify iatrogenic CJD. To find cases mimicking CJD-MMiK, we investigated clinical features and pathology of 1,155 patients with diagnosed sporadic CJD or unclassified CJD with and without history of neurosurgery. Patients with history of neurosurgery more frequently had an absence of periodic sharp-wave complexes on electroencephalogram than patients without a history of neurosurgery.