The research of Shunsuke Koga, M.D., Ph.D., is focused on understanding the clinicopathological correlations of tauopathies and α-synucleinopathies, with a particular focus on progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA). Specifically, Dr. Koga investigates how comorbid pathologies, such as TDP-43 and Alzheimer's-type pathology, modify clinical presentations of patients with PSP, CBD and MSA.
Dr. Koga also works on the application of machine learning in neuropathology. Using machine learning techniques and digitalized images of histopathological slides from a collection of Mayo Clinic brain bank specimens, Dr. Koga aims to develop machine learning-based diagnostic models for assisting decision-making in neuropathological diagnosis.
- Red flag features of MSA. A previous study by Dr. Koga reported that only 62% of patients clinically diagnosed with MSA carried actual MSA pathology. This study pointed out the suboptimal sensitivity of the current diagnostic criteria and highlighted the need to revise the criteria for an MSA diagnosis. He is currently investigating the underlying pathology of red flag features, such as cognitive impairment, early or late symptomatic onset, and vertical gaze palsy, that often lead physicians to make non-MSA diagnoses. The ultimate goal of this work is to provide evidence for improving the current diagnostic criteria of MSA.
- Minimal-change MSA. Minimal-change MSA is a rare subtype of MSA that has widespread glial cytoplasmic inclusions without apparent neuronal loss in the cardinal brain regions. Therefore, Dr. Koga is currently investigating the underlying mechanisms of early pathological changes in minimal-change MSA, with the aim of elucidating the trigger of the development of glial cytoplasmic inclusions in the earliest stage of the disease.
- Clinicopathological subtypes of PSP and CBD. Patients with PSP and CBD can develop various clinical presentations, such as Richardson's syndrome, corticobasal syndrome and progressive aphasia. Several studies have shown that the distribution of tau burden and neuronal degeneration are correlated with clinical subtype; however, little is known about the influence of comorbid pathology in these diseases. To clarify whether comorbid pathology modifies clinical presentation, Dr. Koga has investigated the correlations between comorbid pathologies (TDP-43 pathology, Alzheimer's-related pathology) and clinical manifestations in PSP and CBD.
- Machine learning models for diagnosing tauopathies. PSP and CBD show similar pathology characterized by neuronal and glial lesions composed of pathological aggregates of insoluble tau protein. Even though the two diseases have different distributions and morphological features of tau pathology, the neuropathological diagnosis of PSP and CBD is sometimes challenging. To provide objective methods for assisting decision-making in pathological diagnoses, Dr. Koga has been developing image classification models, object detection models and decision tree classifiers to differentiate the two diseases as well as other tauopathies.
Significance to patient care
The ultimate goal of Dr. Koga's work is to elucidate the underlying pathomechanisms of MSA, PSP and CBD to identify potential therapeutic targets of these diseases. In addition, his work aims to optimize the diagnostic criteria of MSA, PSP and CBD, which can improve the quality of future clinical trials of disease-modifying therapy.