Killam Seminar Series: The Immune System Shapes Brain Function

Abstract: Over the past 28 years, we have challenged the dogma of the brain immune isolation, demonstrating that the brain critically depends on innate and adaptive immune cells for its maintenance and repair. Deep understanding of these relationships led us to propose that peripheral immune cells, located in specialized niches at the brain's borders, along with neurons and non-neuronal cells within the brain parenchyma, create an ecosystem that enhances the brain's resilience to continuous and diverse perturbations. We further suggested that symptom onset in dementia could be linked with dysfunction of the communication between the brain and immune system, which enhances the on-going process of inflammation in the brain, the major driver of cognitive deterioration in dementia regardless of its primary cause. Accordingly, we proposed that boosting the immune system could help restore immunity to mitigate neurodegenerative diseases. We found that transiently blocking the inhibitory PD-1/PD-L1 immune checkpoint pathway, initiates an immune response in the periphery, which leads to disease modification within the brain in animal models of Alzheimer’s disease (AD) and tauopathy. The effect is dependent on homing of reparative immune cells, including monocyte-derived macrophages and FoxP3 regulatory T cells. The earliest effect observed in the brain is
the clearance of senescent microglia, with downstream effects on multiple pathological factors, including reduced inflammation, and rescue of synapses and neurons. This approach is currently being evaluated in a clinical trial involving AD patients, utilizing a novel anti-PD-L1 antibody specifically tailored for AD. Overall, our preclinical studies demonstrate the feasibility of treating neurodegenerative diseases by targeting a common immunological protective pathway, regardless of the primary cause of disease, thereby opening new avenues for therapeutic intervention to combat brain diseases.

Bio: Professor of Neuroimmunology at the Weizmann Institute of Science. Schwartz is the world pioneer in breaking the long-held dogma regarding the relationships between the central nervous system and the immune system. She introduced the current understanding that systemic immune cells are guardians of the brain, needed for life-long brain maintenance and repair. Based on her comprehension of the brain-immune relationship, she proposed that senescence or exhaustion of the immune system plays a key role in brain aging, and in exacerbating Alzheimer’s disease (AD) and other forms of dementia. She suggested a novel treatment for AD, currently in clinical trial, to harness the immune system to help the brain. The impact of her scientific insights is reflected in her extensive publication record in leading journals and high citation number (H factor 124, Google Scholar; more than 62,000 citations), and the number of invited lectures that she delivered. Schwartz received numerous prestigious national and international awards for her outstanding achievements. Most recently, in 2019, Schwartz received the EMET prize, one of the most prestigious Israeli awards for academic achievement, and the FENS EJN Award, 2022 for her outstanding contribution to the field of Neuroimmunology. In 2023, she was awarded the Israel Prize in life sciences, an award bestowed by the State of Israel, and regarded as the state's highest honor. She served as elected president of the International Society of Neuroimmunology (2016-2018). Twenty of her former trainees currently hold academic faculty positions in Israel, the USA, UK, Europe and Australia. She is the scientific co-founder of a startup biopharma, ImmunoBrain, which based on her technology, is currently testing an immunotherapy in the UK, Israel and the Netherlands, with the goal of defeating Alzheimer’s disease.

For more information, visit The Neuro's website

Stream online . No registration required.

Know what’s Happening Next — before everyone else does.

Get App

Host or Publisher The Neuro