Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia and one of the leading causes of death worldwide. AD patients show various symptoms including loss of memory and other cognitive abilities, which worsen over time. AD develops from multiple factors rather than single cause, and various risk factors from genetics to environmental factors are being suggested.

Research Interests

1. Pathological Mechanism

Aβ

Amyloid beta (Aβ) is a long-known pathological molecule in AD. Alzlab focuses on its crosstalk with other neurotoxic molecules and its novel role to induce metabolic malfunction.

• The contribution and the mechanism of Aβ on tau propagation
• Detrimental effect of Aβ on adult neurogenesis through mitochondrial stress
• Metabolic dysfunction of microglia induced by chronic Aβ exposure
• Potent undiscovered Aβ receptor

Tau

Tau is another major pathological molecule of AD. Pathological tau aggregates to form NFT in AD brain and is propagated through brain. Hyper-phosphorylated and aggregated tau lead to diverse dysfunctions and damages in brain. Alzlab focuses on pathological mechanisms of tau for these damages and propagation.

• Degradation mechanism of tau to reduce toxicity
• Mechanism of tau propagation
• Tau toxicity on diverse targets

Microglia

Microglia is a brain innate immune cell which plays a critical role in all over CNS health and disease. Especially, many genetic and transcriptomic studies point out microglia as an important player of AD risk and pathogenesis. Alzlab focuses on discovering exact microglia-related pathways and targets to modulate microglial functions using diverse AD model platform

Crosstalk between peripheral immune system and brain in AD

There are several pathways to communicate peripheral blood to brains including blood brain barrier (BBB), glymphatic pathway and blood CSF barrier. Using several pathways, blood immune cells can affect brain functions through cytokines and/or direct contacts.

2. Disease Modeling

Mouse Models of AD

AD mouse models which recapitulate major pathological features of AD patient’s symptoms are used to translate promising biological findings to drug discovery and investigate underlying disease mechanisms. Alzlab uses several mouse models including 5XFAD, ADLP (Alzheimer’s disease like pathology), and several different aspects of mice

Patient-derived Organoid Model of AD

In studies for neurodegenerative disorders, acquiring human brain samples in adequate condition is highly difficult. When samples are scarce, in vitro models generated from human cells that recapitulate pathophysiology observed in patients can be used as alternatives.

• Optimizing iPSC-based organoid model to accurately recapitulate AD pathology
• Discovering underlying molecular mechanisms of AD
• Developing a validation platform to screen potential therapeutic molecules for specific targets

3. Clinical Application

Blood Biomarkers for AD Diagnosis

Accumulation of Aβ and tau occurs in the early stages of AD. It plays critical roles in initiating AD pathogenesis, therefore, many researchers have sought to predict cerebral Aβ or tau deposition using body fluids such as blood, urine, or cerebral spinal fluid (CSF). Alzlab focuses on finding novel blood-based biomarkers, because of their easier accessibility than positron emission tomography (PET) imaging.

• Finding new blood-based biomarkers in AD with state-of-the-art systems
• Detecting existing blood-based biomarkers more accurately and stably
• Long-term tracking observation of blood-based biomarkers
• Establishment of prognostic blood-based biomarker panel for Aβ or Tau deposition

Gut-brain axis

The gut-brain axis (GBA) is a bidirectional link between the central nervous system (CNS) and the enteric system, which affects emotional and cognitive behaviors and brain functions along with peripheral intestinal functions. Recent advances in gut microbiome research have highlighted the importance of gut microbiota in influencing the GBA axis, and gut microbiota is now considered as a promising therapeutic targets for AD. Alzlab focuses on endocrine, immune, metabolic and neural pathways involved in the GBA and to find out cross-talk between the gut microbiota and the GBA in AD.

• Understanding and manipulating the gut microbiota in animal models of AD
• Molecular mechanisms employed by the gut microbiota during AD pathogenesis
• Patient-derived intestinal organoids to identify the beneficial gut microbiota for the prevention and treatment of AD