Guojun Bu (United States of America)
SciNeuro Pharmaceuticals
Neuroscience
Dr. Guojun Bu is the Chief Scientific Officer at SciNeuro Phamaceuticals. He was previously the Chair and an endowed professor in the Department of Neuroscience at Mayo Clinic Jacksonville, and an Associate Director of Mayo Clinic Alzheimer's Disease Research Center. Prior to joining Mayo Clinic in 2010, he was a Professor of Cell Biology and Neuroscience at the Washington University School of Medicine in St. Louis. Dr. Bu is a world leader in the field of apoE and apoE receptors, which play critical roles in the pathogenesis of Alzheimer’s disease. His primary interest is to understand why APOE4 is a strong genetic risk factor for Alzheimer’s disease and related dementias, and how this pathway can be targeted for therapy by studying animal and stem cell-based cellular and organoid models. His research also includes interests in addressing the pathobiology of TREM2 and its risk variants in microglial functions and pathological development. Dr. Bu has received numerous honors and awards including the Zenith Fellows Award from the Alzheimer’s Association, the Established Investigator Award from the American Heart Association, the Investigator of the Year award from the Mayo Clinic, and the MetLife Foundation Award for Medical Research in Alzheimer’s disease. He is an elected Fellow of the American Association for the Advancement of Science (AAAS), an Associate Editor for Science Advances, and the Editor-in-Chief of Molecular Neurodegeneration.

Moderator of 1 Session

 Conference Calendar
PRE CONFERENCE SYMPOSIUM

PRE CONFERENCE SYMPOSIUM 01 - COMMON FEATURES OF NEURODEGENERATIVE DISEASES: EXPLORING THE BRAIN/EYE CONNECTION AND BEYOND : USE IT OR LOSE IT: HOW TINY CHANGES IN ENERGY, METABOLISM AND MITOCHONDRIA CAN LEAD TO NEURODEGENERATIVE DISEASE

Session Time
08:00 - 15:50
Session Type
PRE CONFERENCE SYMPOSIUM
Date
Tue, 28.03.2023
Room
ONSITE - HALL G3
Session Description
This day-long, CME credit-eligible workshop will provide participants with an understanding of the common and distinct features of neurodegenerative diseases, which include not only those affecting the brain, such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, vascular dementia, frontotemporal dementia, and mixed dementia; but also the ocular diseases including age-related macular degeneration, glaucoma, diabetic retinopathy, and inherited retinal degenerative diseases. Some questions that will be addressed during this fourth pre-symposium workshop, starting from small (Section 1. Mitochondria In Health and Neurodegeneration; and Section 2. Glucose and Lipid Metabolism) and ending with a more wholistic (Section 3. System-level Energy Dysfunction and Metabolic Disorders) point of view: •Why does the nervous system (including the brain and eyes) have a unique energy demand? •How can one evaluate metabolic fitness? •How can only tiny changes in energy, metabolism and/or mitochondria lead to neurodegenerative disease?•Is there a definite ‘tipping point’ that could be prevented in humans to delay onset of disease?•What role do comorbidities, like diabetes and other insulin/energy/metabolism-dysfunction diseases, play in neurodegenerative diseases?•How can one study this in living humans? •Are there common elements across these diseases that could give a clue to preventions and future treatments?Section 1 Summary: Mitochondria are essential organelles that regulate multiple processes essential for neuronal function including metabolic balance, intracellular calcium homeostasis, production of reactive oxygen species, and apoptotic signaling. Accumulating evidence indicates that mitochondrial defects play a central role in the pathogenesis of neurodegenerative diseases. This session will cover new insights into mitochondrial dynamics, trafficking, transmitophagy, and damage as well as novel therapeutic strategies to increase mitochondrial health in eye and brain diseases.Section 2 Summary: Individual cell-types in the brain have unique energy requirements and unique roles in meeting the energetic demands placed on the brain. Disruption in cellular cross-talk and cell-autonomous energy occur during the setting of neurodegenerative disease. A more refined disruption of the cellular and intercellular metabolic defects will likely offer new insights into neurodegenerative disease and perhaps illuminate novel therapeutic approaches.Section 3 Summary: Metabolic conditions and diabetes are risk factors for both Alzheimer’s disease and eye diseases. In addition to hypoperfusion restricting blood flow, they also impact brain energy metabolism including insulin signaling and glucose utilization. In this section, the speakers will discuss how brain metabolism and insulin signaling are impaired in these neurodegenerative conditions and how these pathways can be targeted for therapy to treat brain and eye diseases, and to promote healthy brain aging.

Supported with an educational grant by BrightFocus

Chair(s)

Presenter of 4 Presentations

 Conference Calendar

CLOSING REMARKS

Session Name
3010 - PRE CONFERENCE SYMPOSIUM 01 - COMMON FEATURES OF NEURODEGENERATIVE DISEASES: EXPLORING THE BRAIN/EYE CONNECTION AND BEYOND : USE IT OR LOSE IT: HOW TINY CHANGES IN ENERGY, METABOLISM AND MITOCHONDRIA CAN LEAD TO NEURODEGENERATIVE DISEASE (ID 1)
Session Type
PRE CONFERENCE SYMPOSIUM
Date
Tue, 28.03.2023
Session Time
08:00 - 15:50
Room
ONSITE - HALL G3
Presenter
Lecture Time
15:20 - 15:50

CENTRAL AND PERIPHERAL APOE IN ALZHEIMER’S DISEASE

Session Name
3710 - SYMPOSIUM: APOE MECHANISMS AND TREATMENT STRATEGIES (ID 69)
Session Type
SYMPOSIUM
Date
Thu, 30.03.2023
Session Time
16:20 - 18:20
Room
ONSITE - HALL F4+F5
Presenter
Lecture Time
16:35 - 16:50

Abstract

Abstract Body

Central and Peripheral ApoE in Alzheimer’s Disease

SciNeuro Pharmaceuticals, Rockville, MD, USA

The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). In the central nervous system (CNS), apoE4 inhibits the clearance and promotes the aggregation of amyloid-β (Aβ), and has several Aβ-independent effects. ApoE is also abundantly expressed in peripheral tissues including liver where it mediates plasma lipid metabolism. APOE4 carriers have increased risk for hypercholesterolemia and atherosclerosis. To differentiate apoE functions in CNS and periphery, we developed cell type-specific and inducible mouse models expressing apoE isoforms in individual cell types. Some of these mice were further bred to the background of amyloid model APP/PS1 mice. When apoE isoforms were expressed in astrocytes using GFAP-Cre driver, we found that apoE3 but not apoE4 improved synaptic functions and memory performance, whereas apoE4 but not apoE3 inhibited Aβ clearance and accelerated amyloid deposition. Interestingly, expression of apoE4 prior to amyloid deposition had a much greater impact on amyloid pathology than that during the rapid growth period. When apoE isoforms were expressed by microglia with Cx3cr1-Cre driver, we again found apoE3 but not apoE4 enhanced synaptic functions and memory performance. However, different from astrocytic expression, apoE3 but not apoE4 reduced amyloid deposition likely by enhancing microglial clustering and phagocytic function. More interesting, when apoE isoforms were expressed exclusively in the periphery by liver hepatocytes in the Apoe-knockout background, apoE4 inhibited synaptic function, impaired cognition, and was associated with compromised blood-brain barrier integrity and vascular function. These results provide mechanistic insights as to how apoE4 increases the risk for AD through both central and peripheral effects, and what we need to consider when developing apoE isoform-specific targeted therapies.

Hide

GENERAL DISCUSSION

Session Name
3010 - PRE CONFERENCE SYMPOSIUM 01 - COMMON FEATURES OF NEURODEGENERATIVE DISEASES: EXPLORING THE BRAIN/EYE CONNECTION AND BEYOND : USE IT OR LOSE IT: HOW TINY CHANGES IN ENERGY, METABOLISM AND MITOCHONDRIA CAN LEAD TO NEURODEGENERATIVE DISEASE (ID 1)
Session Type
PRE CONFERENCE SYMPOSIUM
Date
Tue, 28.03.2023
Session Time
08:00 - 15:50
Room
ONSITE - HALL G3
Presenter
Lecture Time
14:50 - 15:20

WELCOME AND INTRODUCTION INCLUDING WORKSHOP GENERAL DISCUSSION PRIMER

Session Name
3010 - PRE CONFERENCE SYMPOSIUM 01 - COMMON FEATURES OF NEURODEGENERATIVE DISEASES: EXPLORING THE BRAIN/EYE CONNECTION AND BEYOND : USE IT OR LOSE IT: HOW TINY CHANGES IN ENERGY, METABOLISM AND MITOCHONDRIA CAN LEAD TO NEURODEGENERATIVE DISEASE (ID 1)
Session Type
PRE CONFERENCE SYMPOSIUM
Date
Tue, 28.03.2023
Session Time
08:00 - 15:50
Room
ONSITE - HALL G3
Presenter
Lecture Time
08:00 - 08:15