Lecture Summary

The neuroanatomical origin of Parkinson’s disease (PD) refers to the initial site of Lewy pathology (LP), the pathognomonic hallmark of PD, and the subsequent propagation pattern of this pathology. Traditionally, the brainstem nuclei, as described in the Braak staging system proposed in 2003, were considered the initial sites within the brain. However, accumulating evidence has since pointed to alternative origins, including the olfactory bulb and other regions of the brain. In parallel, growing attention has been directed toward the peripheral nervous system, particularly the gastrointestinal tract, as a possible starting point of LP in PD. This has fueled ongoing debate over whether LP progresses from the gut to the brain or vice versa. This lecture aims to provide a comprehensive overview of the current evidence regarding the neuroanatomical origin of PD from a pathological perspective. By integrating recent advances and diverse findings, this presentation highlights the heterogeneity of PD pathogenesis and offers insights that may guide future diagnostic and therapeutic approaches.

Lecture Summary

As global populations age, neurodegenerative diseases, particularly synucleinopathies, have garnered significant attention regarding early diagnosis, intervention, and prevention during the prodromal stages. The complex multifactorial etiology, heterogeneous neuropathology, and unclear progression trajectories of synucleinopathies pose considerable challenges to effective early intervention.

This talk will explore current knowledge on identifying at-risk and prodromal populations for synucleinopathies, focusing specifically on REM sleep behavior disorder (RBD) as a critical clinical prodromal marker. Innovative study designs, such as familial cohort studies of RBD, alongside novel technologies like digital-based screening and emerging biomarkers such as gut microbiota, hold promise for cost-effective community screening of at-risk individuals. Additionally, a deeper understanding of long-term disease trajectories and clinically relevant heterogeneities of RBD may enhance personalized prevention and intervention strategies. Despite recent advances in elucidating the pathophysiology of RBD and synucleinopathies, the efficacy of existing disease-modifying therapies remains limited. There is a timely need for the development of novel screening , monitoring, and interventional therapies and active clinical trials targeting high-risk populations, especially RBD and prodromal RBD, who are at the early and potentially preventable stages of the synucleinopathy neurodegeneration

Lecture Summary

Parkinson’s disease is a complex and heterogeneous neurodegenerative disorder, with emerging evidence pointing to diverse cellular origins and disease mechanisms. These include distinct contributions from dopaminergic neurons, glial cells, and peripheral systems, such as the gut and immune system. This plenary lecture will explore how advances in understanding the cellular and molecular underpinnings of Parkinson’s disease are reshaping the landscape of disease-modifying therapy development. A focus will be placed on key cellular pathways implicated in the pathobiology of Parkinson’s disease, including protein aggregation, lysosomal dysfunction, mitochondrial stress, and neuroinflammation, and how they inform current therapeutic strategies. The lecture will also provide an overview of recently completed and ongoing clinical trials targeting these mechanisms, particularly those in phase 2 and 3 development. The objective is for attendees to gain a clearer understanding of how evolving insights into the cellular origins of Parkinson’s disease are guiding translational efforts and what this may mean for clinical practice in the coming years.

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Lecture Summary

In human studies, clinically diagnosed Parkinson’s disease has been associated with exposure to environmental toxicants including certain pesticides, chlorinated solvents and air pollution as well as with life style factors such as physical inactivity. In a few human studies, a synuclein abnormality has been confirmed by biomarker or postmortem exam, but in most cases synuclein pathology has been assumed based on clinical features. In the laboratory, many of these toxicants have been shown to cause synuclein pathology. This lecture will provide an overview of environmental factors associated with synucleinopathies in human populations and explore studies of the combined effects of environmental factors, as well as the effects of environmental plus genetic factors, as triggers for synucleinopathy.

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I will talk about early signs and symptoms of PSP with time course of disease progression.
Interesting pictures and video clips will be included in the lecture.

Lecture Summary

Tauopathies, encompassing Alzheimer’s disease and various frontotemporal dementias, are defined by the pathological conversion of tau from a soluble microtubule-associated protein into insoluble aggregates. While neurons are traditionally viewed as the main locus of this transformation, recent studies demonstrate that tau pathology originates from, and is shaped by, multiple cellular populations in the brain.

Within neurons, abnormal post-translational modifications and structural misfolding generate oligomeric tau species that act as seeds for further aggregation and synaptic propagation. Astrocytes, far from being mere supportive cells, sequester extracellular tau, yet often fail to degrade it efficiently, thereby fostering local toxicity. Oligodendrocytic tau inclusions compromise myelin stability and contribute to white matter decline, highlighting their role in disease beyond axonal support. Microglia initially mitigate pathology through phagocytic clearance but may later exacerbate spread by releasing tau-containing vesicles and sustaining neuroinflammation.

These findings position tauopathy as a disorder emerging from intercellular interactions rather than a neuron-restricted defect. Recognizing cell type–specific contributions reframes therapeutic strategies: targeting neuronal misfolding, augmenting astrocytic clearance, protecting oligodendrocyte function, and recalibrating microglial activity. Understanding the diverse cellular origins of tau pathology will be pivotal for precision medicine approaches to neurodegeneration.

Lecture Summary

Developments in genetics have provided insights into the biology and early diagnosis of PSP and other tauopathies. Efforts to understand these disorders are progressing on a global basis. New developments in high throughput biomarker assays and in the development of protein / aggregation assays are also showing promise in early diagnosis but also showing the extent of overlap and co-pathology across disease..

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Overview of neuronal and non-neuronal mechanisms that contribute to a-synuclein-induced neurodegeneration and highlight of promising therapeutic approaches that target pathological α-synuclein.

Lecture Summary

In this presentation, I will present on cell therapy research for Parkinson's disease using stem cells. I will especially focus on clinical trials using embryonic stem cells (ESCs), which have recently attracted much attention, and compare them with clinical studies using iPSCs. I will also discuss the current status and future prospects of cell therapy for Parkinson's disease, which has a long history.

Lecture Summary

While Deep Brain Stimulation (DBS) is an established symptomatic therapy for Parkinson's disease and other movement disorders, its potential to stop or slow disease progression remains a promising yet controversial field. Current treatments manage symptoms but do not offer neuroprotection or alter the underlying disease course, which is characterised by protein aggregation and selective neuronal death. The core of Parkinson's pathology involves alpha-synuclein oligomers and fibrils, which cause cytotoxicity driving neurodegeneration and disease progression.
This talk will explore the potential to repurpose DBS as a disease-modifying therapy by directly regulating this molecular pathology. The clinical data supporting this concept is currently limited and its investigation is complicated by factors such as biologically heterogeneous patient populations and a lack of definitive biomarkers for disease progression. Further work is required to understand the mechanisms by which DBS might influence alpha-synuclein oligomerization, possibly via cellular pathways like the proteasome or lysosome. Realising the neuroprotective promise of DBS will necessitate revisiting pre-clinical models and refining stimulation parameters, surgical targets, patient selection, and the timing of intervention.