Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN-TU-001 trial.

Introduction: Monoclonal anti-amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD).

Methods: In the DIAN-TU-001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [C]-Pittsburgh compound-B (PiB) positron emission tomography (PET), [F]-fluoro-2-deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI).

Effect of corrections for renal function on plasma phosphorylated tau performance for Alzheimer's disease.

BackgroundBlood-based biomarkers (BBMs), including plasma phosphorylated tau (pTau), have been considered as a promising, less-invasive tool for detecting Alzheimer's disease (AD) pathology in real-world applications. Plasma pTau levels are known to be elevated in individuals with chronic kidney disease, which may require caution when corrected for renal function since it alters testing performance-decreased sensitivity and increased specificity.ObjectiveWe aimed to quantify how correcting for renal function affects BBM test performance.

Audio review as a measure of quality assurance and control of cognitive assessments in Alzheimer's disease studies: An experience from Japanese Trial-Ready Cohort Study.

Background: Clinical trials targeting preclinical Alzheimer's disease (AD) require accurate cognitive assessments to detect subtle changes over time. Audio review of assessment sessions has been proposed as a quality assurance (QA) and control (QC) measure, yet evidence regarding its effectiveness remains limited.

Objective: We aim to investigate how audio review contributes to the QA/QC process.

Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.

Clinical trials of anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal fluid (CSF) Aβ42/40. However, these biomarkers measure brain Aβ deposits indirectly and/or incompletely. In contrast, neuropathologic assessments allow direct investigation of treatment effects on brain Aβ deposits-and on potentially myriad 'downstream' pathologic features.

Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.

Introduction: Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited "therapeutic time window," after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities.

Clinicopathological features of anti-HMGCR and anti-SRP myopathies that do not satisfy the EULAR/ACR criteria of inflammatory myopathies.

Objectives: The clinicopathological features of immune-mediated necrotizing myopathy (IMNM) sometimes mimic muscular dystrophy, complicating accurate diagnosis. The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria of idiopathic inflammatory myopathies (IIMs) are superior in terms of sensitivity and specificity; however, the sensitivity is reported to be relatively low in IMNM. We examined the clinicopathological characteristics and the prognoses of anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody-positive and anti-signal recognition particle (SRP) antibody-positive cases that do not satisfy the EULAR/ACR classification criteria.

Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering.

The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering.

Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies.

Introduction: Blood-based biomarkers (BBBMs), including plasma amyloid beta (Aβ) or phosphorylated tau (p-tau), combined with apolipoprotein E () testing, are anticipated to serve as prescreening tools before amyloid positron emission tomography (PET) for recruiting participants for Alzheimer's disease (AD) prevention studies. The predictive efficacy and cost-effectiveness of prescreening may vary with different testing combinations, sequences, and cutoff levels.

Methods: We conducted a simulation study utilizing data from our ongoing Japanese Trial-Ready Cohort (J-TRC) onsite study ( = 202) recruited online.

Bjerkandera adusta Fungi as Causative Agent of Invasive Chronic Rhinosinusitis.

We report an invasive mycosis case in Japan caused by Bjerkandera adusta, a fungal species not previously reported as a causative pathogen of invasive mycosis. B. adusta was identified by using phylogenetic analysis.

Cognitive function instrument-based anosognosia to predict amyloid status.

Anosognosia, a lack of self-awareness regarding cognitive dysfunction, often accompanies the progression of Alzheimer's disease (AD) pathology. This study explored the relationship between AD pathology and anosognosia measured by discrepancies in Cognitive Function Instrument (CFI) scores, as rated by participants and their study partners (SP). Using mixed-effects models on non-demented participant data, the results revealed that lower self-reported CFI score compared to SP ratings was significantly associated with positive amyloid PET results (odds ratio 1.

Robot-Assisted CT-Guided Biopsy with an Artificial Intelligence-Based Needle-Path Generator: An Experimental Evaluation Using a Phantom Model.

Purpose: To investigate the feasibility of a robotic system with artificial intelligence-based lesion detection and path planning for computed tomography (CT)-guided biopsy compared with the conventional freehand technique.

Materials And Methods: Eight nodules within an abdominal phantom, incorporating the simulated vertebrae and ribs, were designated as targets. A robotic system was used for lesion detection, trajectory generation, and needle holder positioning.

[A case of anti-ganglioside antibody-positive Guillain-Barré syndrome with asymmetrical muscle weakness throughout the course of the disease].

A 56-year-old woman who presented with left drop foot and low back pain a week after the onset of diarrhea. Neurological symptoms progressed for a week and gradually improved thereafter. No weakness was observed in upper limbs and clearly asymmetrical muscle weakness was observed in left lower limbs during the course of the disease.

Activation of fibroblasts by plasma cells via PDGF/PDGFR signaling in IgG4-related sialadenitis.

IgG4-related sialadenitis (IgG4-SA) is one of the IgG4-related disease. The histological features of IgG4-SA include dense lymphoplasmacytic infiltrates and fibrosis. This study aimed to reveal the involvement of plasma cells in the development of fibrosis and the mechanism underlying fibrosis in IgG4-SA.

-ε4 allele[s]-associated adverse events reported from placebo arm in clinical trials for Alzheimer's disease: implications for anti-amyloid beta therapy.

-ε4 allele[s] is a risk factor for Alzheimer's disease (AD) and Amyloid-Related Imaging Abnormalities (ARIA) in anti-amyloid beta therapy, and is also associated with cerebrovascular risk factors such as hyperlipidemia or atherosclerosis. During AD clinical trials, -ε4 carriers may experience neuropsychiatric adverse events (AEs) related to these risks, complicating the differentiation of ARIA from cerebrovascular events based on symptoms. This study aimed to examine the hypothetical impact of considering the -ε4 allele's risk for non-ARIA AEs during AD clinical trials.

Photon-counting detector CT with an ultra-low-dose contrast media to diagnose a renal pseudoaneurysm: A case report.

A 75-year-old male, weighing 71 kg, was admitted to our institution with anemia related to a subcapsular hematoma after accidental extraction of a nephrostomy catheter. While the patient exhibited the progression of chronic kidney disease, he was not yet on dialysis. His serum creatinine level increased to 6.

Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.

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 in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.

Methods: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study.

Simplifying Alzheimer's Disease Monitoring: A Novel Machine-Learning Approach to Estimate the Clinical Dementia Rating Sum of Box Changes Using the Mini-Mental State Examination and Functional Activities Questionnaire.

Background: Primary outcome measure in the clinical trials of disease modifying therapy (DMT) drugs for Alzheimer's disease (AD) has often been evaluated by Clinical Dementia Rating sum of boxes (CDRSB). However, CDR testing requires specialized training and 30-50 minutes to complete, not being suitable for daily clinical practice.

Objective: Herein, we proposed a machine-learning method to estimate CDRSB changes using simpler cognitive/functional batteries (Mini-Mental State Examination [MMSE] and Functional Activities Questionnaire [FAQ]), to replace CDR testing.

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.

Importance: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD).

Objective: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment.

Design, Setting, And Participants: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD.

Neighboring macrophage-induced alteration in the phenotype of colorectal cancer cells in the tumor budding area.

Background: A higher number of tumor buds in the invasive front of colorectal cancer (CRC) specimens has been shown to contribute to a poor prognosis in CRC patients. Because macrophages (Mφs) have been demonstrated to alter the phenotype of cancer cells, we hypothesized that the phenotype of CRC cells in the tumor budding (TB) area might be changed by the interaction between CRC cells and Mφs.

Methods: We assessed the expression of topoisomerase 1 in CRC cells to estimate the acquisition of chemoresistance in CRC.

Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease.

Introduction: Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.

Methods: We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker.

[A case of tuberculous meningitis diagnosed early by direct Loop-Mediated Isothermal Amplification (LAMP) method using centrifuged medium of cerebrospinal fluid culture].

Tuberculous meningitis (TBM) is a central nervous system infection with a high mortality rate and requires early diagnosis and treatment. Identification of Mycobacterium tuberculosis in the cerebrospinal fluid is of primary importance in the diagnosis of TBM, however, conventional methods have some disadvantages: Rapid results tests such as smear and regular PCR method do not have sufficient diagnostic sensitivity; Nested PCR, which is one of the most sensitive tests, is not available in all facilities; Culture tests require a long period of 4-8 weeks for results. Here we report a case of TBM, diagnosed 14 days earlier than culture test by direct Loop-Mediated Isothermal Amplification (LAMP) method using centrifuged medium of cerebrospinal fluid (day 18) culture.