Pathobiology of APOE in aging and Alzheimer’s disease

Guojun Bu, PhD

• Hong Kong University of Science and Technology, Hong Kong
• Head and Chair Professor, Division of Life Science
• Lo Ka Chung Charitable Foundation Professor of Science
• Co-Director of Brain and Intelligence Research Institute
• Editor-in-Chief, Molecular Neurodegeneration

• Abstract
  Alzheimer’s disease (AD) is the leading cause of dementia in our aging society. Despite progress in understanding the pathological events, the complex molecular mechanisms underlying AD development remains a critical barrier to effective therapy. The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for AD compared to the common ε3 allele or the protective ε2 allele. In the brain, apoE4 inhibits the clearance and promotes the aggregation of amyloid-β (Aβ) and has several Aβ-independent effects including impaired lipid transport, compromised cerebrovascular integrity and synaptic function, and heightened neuroinflammation. In this lecture, I will discuss our current understanding of how APOE impacts AD risk with a focus on our own studies using animal models and iPSC-derived cellular and organoid models. Specifically, using human APOE allele-specific and cell type-specific mouse models, we found that apoE isoforms expressed in different cell types in the brain, vasculature, and periphery differentially modulate brain cognition and AD pathology. Highlights will include the effects of peripheral apoE and microglial apoE in brain function and AD pathogenesis in an isoform-dependent manner. These insights from our group and others are essential for designing individualized, genotype-specific therapies targeting the APOE pathway.

Tissue biomarkers in Parkinson’s disease and its implication

Beomseok Jeon, MD, PhD

• Director, BJ Center for comprehensive Parkinson care and rare movement disorders
• Chung-Ang University Health care system, Hyundae Hospital
• Professor Emeritus, Seoul National University
• Treasurer, International Parkinson and Movement Disorder Society
• Chair of the Local Organizing Committee, International Congress of Parkinson’s disease and Movement Disorders 2026
• Honorary Member of Japanese Society of Neurology
• Stanley Fahn Lecture Award from Movement Disorder Society
• Lifetime Achievement Award from International Association of Parkinson and Related Disorders

• Abstract
  Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms arising from dopaminergic neuron loss in the substantia nigra. Identifying reliable tissue biomarkers offers potential for early diagnosis, monitoring disease progression, and evaluating therapeutic interventions. Recent research highlights biomarkers such as α-synuclein aggregates, neuroinflammatory markers, mitochondrial dysfunction proteins, and altered lipid metabolism profiles in brain and peripheral tissues. These findings provide insight into PD pathophysiology and may bridge molecular changes with clinical phenotypes. Further validation and standardization of biomarker assays could transform PD management by enabling more targeted and personalized therapeutic approaches.

Scaling AI for Safety and Impact: Our Journey at Duke Health

Eric Poon, MD, MPH

• Chief Health Information Officer (CHIO) & Primary Care Internist, Duke University Health System
• Professor of Medicine & Informatics, Duke University School of Medicine
• Inaugural Program Director, ACGME-accredited Clinical Informatics Fellowship Program
• Associate Editor, Journal of the American Medical Informatics Association (JAMIA, Since 2017)
• Elected Fellow (FACMI), American College of Medical Informatics (Elected 2018)

• Abstract
  The rapid advancement of artificial intelligence presents both transformative opportunities and significant risks for healthcare organizations. In this session, Dr. Eric Poon, Chief Health Information Officer at Duke Health, details how his institution established a comprehensive AI governance framework while simultaneously deploying AI solutions that deliver measurable clinical, operational, and financial outcomes. Duke Health's Algorithm-Based Clinical Decision Support Oversight Committee, formed in 2021, now oversees more than 100 registered AI tools — ensuring each meets rigorous standards for safety, equity, regulatory compliance, and demonstrated value. The presenters share enterprise-scale results: ambient AI documentation reduced clinician burnout and increased ambulatory productivity by over 9%; Duke's EHR Scout platform decreased chart-review time by 39% and cognitive load by 40% in a blinded crossover trial; and revenue cycle AI tools identified more than $18 million in billing impact through automated coding and clinical documentation improvement. This session provides a replicable blueprint for health system leaders seeking to scale AI responsibly — from standing up oversight structures and navigating the evolving regulatory landscape to quantifying return on investment and sustaining clinician trust.

Managing Seizures and Status Epilepticus in the ICU

Ji Yeoun Yoo, MD

• Professor of Neurology, Icahn School of Medicine at Mount Sinai
• Director, Epilepsy Fellowship Program
• System-wide Quality Lead for Epilepsy
• Medical Director, Epilepsy Monitoring Unit at Mount Sinai Hospital

• Abstract
  Status epilepticus remains one of the most time-sensitive emergencies in neurocritical care, yet management continues to evolve as new evidence reshapes long-standing practice. This talk presents an evidence-based framework for status epilepticus in the ICU, from initial stabilization through super-refractory disease. We review the pharmacologic rationale for early, adequately dosed benzodiazepine therapy and revisit the ESETT trial's conclusion that no second-line agent is superior among levetiracetam, fosphenytoin, and valproate, reframing agent selection around patient-specific factors rather than presumed potency. The essential role of continuous EEG in detecting nonconvulsive seizures, which are common yet easily missed in critically ill and sedated patients, and in guiding anesthetic titration is discussed alongside third-line strategies for refractory disease.
  Particular attention is given to recent developments: the expanding role of ketamine as a mechanistically distinct addition to the refractory-status armamentarium, emerging immunotherapy protocols (anakinra, tocilizumab) for NORSE and FIRES, and the wave of updated 2025 guidelines from the UK Intensive Care Society, Neurology, and Lancet Neurology calling for modernized definitions and escalation pathways. Attendees will leave with a practical, up-to-date algorithm for status epilepticus management they can apply directly at the bedside.

Blood-Based Biomarkers for AD Diagnosis and Treatment: Practical Implementation in Austria

Elisabeth Stögmann, MD

• Associate Professor, Medical University of Vienna
• Head of the Outpatient Memory Clinic
• Senior Neurologist specializing in Alzheimer’s disease
• Principal Investigator in national and international research projects and clinical trials
• President, Austrian Alzheimer Society
• Author of over 100 peer-reviewed publications

• Abstract
  Blood-based biomarkers are rapidly transforming the diagnostic landscape of Alzheimer’s disease (AD), offering the potential for earlier, more accessible, and less invasive detection of AD pathology. With the increasing availability of disease-modifying therapies, their integration into clinical practice is becoming particularly relevant, both for establishing a timely and accurate diagnosis and for identifying patients who may benefit from treatment.
  This presentation will provide a practical perspective on the implementation of blood-based biomarkers for AD in Austria. It will discuss their current and emerging role within the diagnostic pathway, including their use in memory clinics and their integration with clinical assessment, neuropsychological testing, cerebrospinal fluid biomarkers, and molecular imaging. Particular attention will be given to phosphorylated tau biomarkers, including p-tau217, and their potential to support diagnostic decision-making and streamline access to confirmatory testing.
  Beyond diagnostic performance, the presentation will address key practical considerations for real-world implementation, including patient selection, interpretation of results, appropriate cut-offs, pre-analytical factors, and the need for clear diagnostic algorithms. Finally, the Austrian perspective will be discussed in the context of evolving European recommendations and the anticipated introduction of disease-modifying AD treatments into routine clinical care.

Immune Dysregulation in Myasthenia Gravis and Neuroimmune Disorders: Insights from Single-Cell and Systems Immunology

Yoshiaki Yasumizu, MD, PhD

• Associate Research Scientist, Department of Neurology, Yale School of Medicine, Yale University
• Physician-Scientist, Neuroimmunology Research
• Expert in Single-Cell Genomics, Spatial Transcriptomics, and Computational Immunology

• Abstract
  Myasthenia gravis (MG) is an autoimmune neurological disease caused by antibodies against proteins at the neuromuscular junction. MG is frequently associated with thymoma or thymic hyperplasia, but how abnormal thymic tissue promotes autoantibody production has remained unclear.  
  
  Using single-cell RNA sequencing of MG-associated thymoma, we identified neuromuscular medullary thymic epithelial cells (nmTECs), a distinct epithelial population that ectopically expresses neuromuscular molecules. These cells may provide a local source of disease-relevant autoantigens. The same tissue also showed immune features linked to antibody production, including ectopic germinal centers, T follicular helper cells, dendritic cells, and B-cell responses.  
  
  Spatial transcriptomic analysis further showed that these disease-related signals form organized tissue niches. In MG-associated thymoma, nmTECs are enriched near the cortico-medullary junction, while medullary regions contain B cells, germinal center-like structures, chemokines, dendritic cells, and regulatory T cells. Similar structures are also observed in MG-associated thymic hyperplasia.  
  
  These findings suggest that MG can be understood as a disease shaped by local thymic tissue architecture, where autoantigen-expressing epithelial cells and B-cell-supporting immune niches coexist. In this lecture, I will discuss how single-cell and spatial analyses have advanced our understanding of thymic local immunity in MG, and how identifying disease-relevant cells and immune niches in patient tissues may contribute to MG pathogenesis and biomarker discovery.

Beyond CGRP-Targeted Therapy in Migraine: What Comes Next?

Eiichiro Nagata, MD, PhD

• Executive Director, Tokai University Hospital
• Senior Chair of Internal Medicine,
• Professor and Chair, Department of Neurology, Tokai University School of Medicine
• Director, Comprehensive Stroke Center

• Abstract
  The development of calcitonin gene-related peptide (CGRP)-targeted therapies has revolutionized migraine treatment and provided compelling evidence for the central role of the trigeminovascular system. However, not all patients respond adequately to CGRP-targeted therapies, suggesting that migraine pathophysiology extends beyond a single neuropeptide pathway. This presentation will explore emerging molecular mechanisms and therapeutic targets beyond CGRP. First, I will discuss pituitary adenylate cyclase-activating polypeptide (PACAP), a key mediator of trigeminovascular activation and an emerging therapeutic target. I will then address amylin, a CGRP-related peptide that may contribute to migraine through overlapping but distinct signaling pathways. In addition, the roles of protease-activated receptor 2 (PAR2) and transient receptor potential (TRP) channels in neurogenic inflammation and trigeminal sensitization will be discussed.
  Finally, I will focus on photophobia and the emerging concept of the melanopsin–intrinsically photosensitive retinal ganglion cell (ipRGC)–PACAP pathway. This pathway may provide a link between abnormal light processing and trigeminovascular activation, potentially connecting photophobia with PACAP and CGRP signaling.
  Together, these pathways suggest that migraine should be viewed as an interconnected neuropeptide, sensory, and neuroimmune network. Understanding this network may open the way toward new therapeutic targets and more mechanism-based, personalized treatment strategies beyond CGRP.

Diet-Gut-Brain in Parkinson's Disease

Masaaki Hirayama, MD, PhD

• Chubu University, Graduate School of Life and Health Sciences
• Professor, Department of Rehabilitation Sciences
• Joint researcher of Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine
• Neurologist
• Local Director of Japan Parkinson’s Disease Association (JPDA)

• Abstract
  The relationship between neurological disorders and the gastrointestinal system has attracted increasing attention, particularly in the field of neurodegenerative diseases, including dementia and Parkinson’s disease. This review focuses on Lewy body diseases, a broad disease spectrum encompassing PD, dementia with Lewy bodies, and REM sleep behavior disorder. These disorders share a common pathological feature: the accumulation of abnormal intracellular aggregates, known as Lewy bodies, whose major component is α-synuclein.
  In recent years, the gut–brain axis has emerged as an important framework for understanding the pathogenesis of LBDs. Increasing evidence suggests that the formation of pathological α-synuclein in the gastrointestinal tract, alterations in the gut microbiota, impaired intestinal barrier function, and chronic inflammation may contribute to the initiation and progression of pathological changes in the brain. Microbial dysbiosis and changes in microbiota-derived metabolites may influence neuronal function and neuroinflammation through neural, immune, endocrine, and metabolic pathways. This review provides an overview of the relationship between the pathophysiology of LBDs and the gut–brain axis, with particular emphasis on alterations in the gut microbiota and microbial metabolites.
  In addition, we discuss the relationships between dietary patterns and the gut microbiota in South Korea, Taiwan, and Japan.

IICP Management: Clinical Challenges and Pitfalls

Yasuhiro Kuroda, MD, PhD

• Auditor, Japanese Society of Intensive Care Medicine
• Visiting Professor, Faculty of Medicine, Kagawa University
• President, Japan Intensive Care Promotion Organization
• Executive Director, Japan Resuscitation Council
• President, Japan Association of Cerebral Resuscitation and Brain Death

• Abstract
  In managing intracranial pressure (ICP), invasive and continuous ICP monitoring is the standard practice. However, there are situations where invasive ICP monitoring cannot be performed, such as in cases of coagulation disorders, in which case non-invasive ICP monitoring is necessary. Quantitative pupillary measurement (NPi<3) is useful for screening patients who may have elevated ICP. Transcranial Doppler (TCD) is useful for excluding elevated ICP by calculating estimated ICP values (<20.5 mmHg) and may also be useful for screening high-risk patients who may require invasive ICP monitoring. On the other hand, even if TCD results indicate elevated ICP, treatment intervention should not be decided based on this result alone. Optic nerve sheath diameter (ONSD) can detect elevated ICP using a threshold (>5.3 mm), but the threshold varies, making routine use in clinical practice difficult. In recent years, attention has been drawn to the fact that elevated ICP (P2/P1>1) can be predicted by ICP waveform analysis, which measures nanometer-scale displacement of cranial deformation associated with changes in ICP. Non-invasive ICP measurement should be used in conjunction with invasive ICP monitoring, after understanding its characteristics and limitations.

Evolving Landscape of ALS Treatment and Prevention

Ikjae Lee, MD, MSc

• Associate Professor at Columbia University Irving Medical Center, Department of Neurology
• Physician Scientist at Eleanor & Lou Gehrig ALS Center
• Neuromuscular specialist with focused research expertise in ALS and metabolism
• Co-chair of Northeast ALS consortium upper motor neuron and biorepository committees
• Muscle Nerve editorial board member

• Abstract
  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without a cure. Over the past decade, studies of genetic forms of ALS has advanced knowledge of disease pathogenesis and spurred development of gene-targeted therapies. Neurofilament light chain (NfL) is now an established biomarker with diagnostic, prognostic, treatment-response, and predictive utilities, and is increasingly incorporated into clinical trials and patient care. The concept of a prodromal phase has emerged, and studies of presymptomatic individuals have provided a platform for identifying early markers of disease onset before overt symptoms manifest, enabling their inclusion in prevention trials. Tofersen, an SOD1 antisense oligonucleotide, lowers blood NfL levels by half and is associated with functional stabilization and, in some patients, improvement. Ulefnersen, a FUS antisense oligonucleotide, is under investigation in a phase 3 trial. The SILENCE-ALS trial targets TARDBP mutations and may have broader relevance to sporadic ALS, given that TDP-43 pathology is present in 97% of ALS cases. Metabolic alterations, including hypermetabolism, increased fatty acid oxidation, mitochondrial dysfunction, and muscle and fat mass loss, are common in ALS. Preliminary findings from MAPS-ALS, a study of metabolic alterations in presymptomatic and symptomatic ALS, and GLP-1 ALS studies will be presented.