The prospect of immunotherapy to combat Alzheimer's disease and dementia: the key role of the brain's choroid plexus

Date:
12
Tuesday
November
2019
Lecture / Seminar
Time: 12:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Michal Schwartz
Organizer: Department of Brain Sciences
Details: Dept of Neurobiology, WIS
Abstract: The brain is no longer considered a completely autonomous tissue with respect t ... Read more The brain is no longer considered a completely autonomous tissue with respect to its immune activity. Rather, immune surveillance is required for supporting brain functional plasticity and repair. Essential immune cells include the microglia, the resident immune cells of the brain, and circulating immune cells. Both the resident microglia and the circulating immune cells are under tight regulatory control to allow risk-free benefit from immunological interventions. We found that access of circulating immune cells to the brain is controlled by the brain’s epithelial barrier, the blood cerebrospinal barrier. Using immunological and immunogenomic tools, we discovered that in brain aging and under neurodegenerative conditions, this barrier does not optimally function to enable brain repair. We further showed in mouse models of Alzheimer’s disease (AD), that activating the immune system by immunotherapy directed against the inhibitory PD-1/PD-L1 immune checkpoint pathway drives an immune-dependent cascade of processes that start in the periphery and culminate with recruitment of monocyte-derived macrophages to the brain, which contribute to disease modification, reversing and slowing-down cognitive loss, reducing brain inflammation, and mitigating disease pathology in a mouse models of AD and Dementia (tauopathy). Overall, our results indicate that targeting the immune system outside the brain, rather than brain-specific disease-escalating factors within the central nervous system, can potentially provide a multi-dimensional disease-modifying therapy for AD and dementia.
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