10:00 – 10:30

WELCOME AND INTRODUCTION INCLUDING WORKSHOP GENERAL DISCUSSION PRIMER
D. Bovenkamp ,G. Bu, A. Di Polo, T. Golde

WHAT IS CELLULAR SENESCENCE AND WHAT IS ITS IMPACT IN NEURODEGENERATIVE DISEASES OF THE BRAIN AND EYE?
Chair: T. Golde, USA

Section 1 Summary:
Many age-related neurodegenerative diseases, like Alzheimer’s, Parkinson’s, macular degeneration and glaucoma, share pathogenic elements that accumulate over time at the genetic, molecular, and cellular levels, including an increase in cellular senescence. When cells of the brain and retina senesce, they transition into a permanent, irreversible state of cell cycle arrest that can reduce the function and regenerative potential of these terminally differentiated tissues as well as increase a senescent pro-inflammatory phenotype. Reducing cellular senescence could be a promising approach to prevent the loss of cells and the alteration of their function. The speakers in this section will define the phenotype and pathology of senescent cells in dementia and blinding diseases, and outline the genetics, mechanisms, systems pharmacology, and potential treatment methods.

10:30 – 10:50

NOVEL TREATMENT MODELS ATTACKING SENESCENCE IN ALZHEIMER’S DISEASE

Darren Baker (USA)

10:50 – 11:10

CELLULAR SENESCENCE IN THE EYE – FOCUS ON RETINA

Dorota Skowronska-Krawczyk (USA)

11:10 – 11:30

AGEING, SENESCENCE AND NEURODEGENERATIVE DISEASES

João Pedro de Magalhães, UK

11:30 – 11:50

SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE AND PATHOLOGICAL ANGIOGENESIS IN RETINOPATHY
Mike Sapieha, Canada

HOW DOES RESILIENCE, FROM GENETICS TO ENVIRONMENTAL, AT THE CELLULAR, SYSTEMS, OR POPULATION LEVELS, PLAY A ROLE IN REDUCING RISK FOR NEURODEGENERATIVE DISEASE?
Chair: G. Bu, USA

Section 2 Summary:
Why do some people escape disease? Resilience occurs when risk factors or pathology are present, but that person doesn’t succumb to clinically detectable disease. At the cellular level, differential expression of genes, proteins and/or epigenetic markers makes one vulnerable or resistant to different eye or brain diseases. At the organismal level, how does one define that a tissue has pathology and how is that related to the ‘tipping point’ to develop cognitive or visual issues? At the population level, what are the origins of racial/ethnic, sex-based, environmental and other differences that can lead to one group being more resilient or at-risk than another? It’s more important than ever, when assessing resilience, to pursue a cross-disease, multi-organ, multi-cell type, and systemic approach.

11:50 – 12:10

ASSESSMENT OF DEMOGRAPHIC, GENETIC, AND IMAGING VARIABLES ASSOCIATED WITH BRAIN RESILIENCE AND COGNITIVE RESILIENCE TO PATHOLOGICAL TAU IN PATIENTS WITH ALZHEIMER DISEASE
Rik Ossenkoppele ,The Netherlands

12:10 – 12:30

RESISTANCE, RESILIENCE, RESERVE AND COMPENSATION

Thomas Montine, USA

12:30 – 12:50

APOE2 AND RARE PROTECTIVE VARIANTS AGAINST ALZHEIMER’S DISEASE: HOW DO THEY DO IT?
G. Bu, USA

12:50 – 13:10

FUNCTIONAL RESILIENCE OF RETINAL GANGLION CELLS DURING MITOCHONDRIAL OXIDANT GENERATION
Steven Barnes, USA

WHY ARE THE VASCULAR COMPONENTS AND BLOOD-BRAIN/BLOOD-RETINA BARRIERS OF THE BRAIN AND EYE IMPORTANT CONTRIBUTORS TO THE TIPPING POINT BETWEEN HEALTH AND DISEASE?
Chair: A. Di Polo, Canada

Section 3 Summary:
Despite recent advances in our understanding of the pathology of cognitive and retinal degenerative diseases, the actual triggers that lead to neurodegeneration are not currently known. One of the ‘tipping points’ for the onset and progression of pathology can be dysfunction of the microvasculature, dysregulation of neurovascular coupling, and alteration of the blood-brain/blood-retinal barriers. Alzheimer’s, glaucoma, and macular degeneration all feature vascular abnormalities, but the full extent to which these factors contribute to the development of disease is not well understood. This session will explore the molecular and cellular mechanisms that could be exploited to better understand the role of microvascular components in the pathophysiology, risk assessment, diagnostic and novel therapeutic targets for brain and eye diseases.

13:10 – 13:30

BIOENGINEERED VASCULAR MODELS FOR DEMENTIA (INVOLVING ENDOTHELIA, SMOOTH MUSCLE, AND ASTROCYTES)
Cheryl Wellington, Canada

13:30 – 13:50

INTERPERICYTE TUNNELLING NANOTUBES: A NEW CONDUIT ESSENTIAL FOR NEUROVASCULAR COUPLING

Luis Alarcon Martinez, Canada

13:50 – 14:10

ISCHEMIA-INDUCED CEREBROVASCULAR DYSREGULATION CONTRIBUTES TO ALZHEIMER’S DISEASE

Anusha Mishra, USA

14:10 – 14:30

BLOOD-BRAIN BARRIER CELLULAR AND MOLECULAR MECHANISMS UNDERLYING NEURODEGENERATION, COGNITIVE DYSFUNCTION AND AD

Berislav Zlokovic, USA

14:30 – 14:50

NEW DYNAMIC ASPECTS OF NEUROVASCULAR COUPLING IN THE HUMAN RETINA, CHOROID AND OPTIC NERVE RELEVANT TO BRAIN NEURO-DEGENERATIONS

Randy Kardon, USA

14:50 – 15:20

Break

15:20– 15:50

LIVE DISCUSSION / Q&A: WHAT IS CELLULAR SENESCENCE AND WHAT IS ITS IMPACT IN NEURODEGENERATIVE DISEASES OF THE BRAIN AND EYE?

15:50 – 16:20

LIVE DISCUSSION / Q&A:HOW DOES RESILIENCE, FROM GENETICS TO ENVIRONMENTAL, AT THE CELLULAR, SYSTEMS, OR POPULATION LEVELS, PLAY A ROLE IN REDUCING RISK FOR NEURODEGENERATIVE DISEASE?

16:20 – 16:50

LIVE DISCUSSION / Q&A:WHY ARE THE VASCULAR COMPONENTS AND BLOOD-BRAIN/BLOOD-RETINA BARRIERS OF THE BRAIN AND EYE IMPORTANT CONTRIBUTORS TO THE TIPPING POINT BETWEEN HEALTH AND DISEASE?

16:50 – 17:20

LIVE GENERAL DISCUSSION: ALL FACULTY

17:20 – 17:30

LIVE CLOSING REMARKS