NICO-Webinar: "Two stories, one message: loss of brain-immune homeostasis threatens brain function" 25/10/22 @ h. 2:00 PM
25/10/22 h. 2:00 pm - Lecture
Stefano Suzzi, Weizmann Institute of Science, Israel
Two stories, one message: loss of brain-immune homeostasis threatens brain functi
Alzheimer’s disease (AD) is anenigmatic neurodegenerative disease, since brain pathology is not sufficient to explain functional loss. The elucidation of the anatomical and functional relationships between the brain and the immune system has revolutionized the concept of “immune privilege”. It is now clear that factors affecting the immunological milieu outside the brain or at its borders also shape the brain’s fate. In one project, we found that high-fat obesogenic diet accelerated disease manifestations in a mouse model of AD (5xFAD). We found that the early onset was linked to systemic CD4+ T-cell deregulation reminiscent of immune aging, and to increased circulating levels of free N-acetylneuraminic acid (NANA).
We demonstrated that NANA could recapitulate diet-induced immune perturbations and accelerate cognitive deterioration when administered to regularly-fed 5xFAD mice.
In a second project, we focused on the choroid plexus (CP) as a key immune gatekeeper of the brain. We show that the CP epithelium expresses the neuronal-selective cholesterol 24-hydroxylase CYP46A1, and that its product 24-hydroxycholesterol (24-OH) can locally suppress immune-related signatures previously associated with cognitive impairment. We found that CYP46A1 expression by the CP is reduced in 5xFAD mice, and that boosting its expression is neuroprotective.
In summary, we propose that therapeutic approaches targeting systemic immunity or the brain’s borders are potentially disease-modifying strategies regardless of primary etiology.
Host: Alessandro Vercelli | webex link