Slide 1: Neuroinflammation in AD. A Dr Jekyll and Mr Hyde story?
novo nordisk* Neuroinflammation in AD. A Dr Jekyll and Mr Hyde story?
Slide 2: AD risk genes indicate the key role of the immune response in disease progression
Q AD risk genes indicate the key role of the immune ola response in disease progression
Slide 3: AD is a complex disease; together with amyloid and tau, neuroinflammation plays a key role
Q AD is a complex disease; together with amyloid and tau, ob Di neuroinflammation plays a key role Reactive oxygen species Excessive synaptic pruning Reduced trophic factors Complement activation Pro-inflammatory cytokines Activated microglia t + Loss of Chemokines homeostatic function + Release of
Slide 4: Brain measurements during life. Biomarkers of AD
Brain measurements during life. Biomarkers of AD Imaging biomarkers nmnyioktiREY CSF biomarkers AB42, AB42/40 Blood biomarkers Neurodegeneration (N) MRI atrophy, FDG PET Total tau, NfL, neurogranin p-tau181, p-tau217, p-tau231 p-tau181, p-tau217, p-tau231 Total:tau..NfL ‘AB, arnoid beta AD, Azheimer
Slide 5: Microglia and astrocytes mount an acute neuroinflammatory response to immune challenges like infections
Q Microglia and astrocytes mount an acute neuroinflammatory ob Bas response to immune challenges like infections Protective, acute neuroinflammation (e.g., to fight an infection)'* Infection Inflammatory Tissue response Inflammation Inflammation orinjury —> response —> andinjuryrepair —> resolves —
Slide 6: Chronic neuroinflammation is a pathological state that can lead to tissue injury and neurodegeneration
Q Chronic neuroinflammation is a pathological state that can lead “ob Bs to tissue injury and neurodegeneration —> e Activated microglia + Dysfunction + Apoptosis = + Synaptic loss + Excessive pro-inflammatory cytokines 5 + Homeostatic function lost Reactive + Excessive glutamate release astrocyte c
Slide 7: Several factors contribute to neuroinflammation
Q Several factors contribute to neuroinflammation ob Bas Biochemical Cellular processes of abnormalities’ neuroinflammation SSG Impaired blood-brai Oxidative stress® Astrocyte end foot vr P= * > Peripheral Perivascular cell >< inflammation* Basal lamina Lumen Endothelial cell ee Risk factors?? Neuro
Slide 8: Key learnings
/ ul key learnings Asustained immune response leading to chronic inflammation is a central feature of neurodegenerative disorders, including Alzheimer’s disease. The role of immune cells (i.e., microglia and astrocytes) in AD is well validated, and supported by genetic, epidemiological, pathology an
Slide 9: References
/ References Bieger A et al. J Prev Alzheimers Dis 2023;10, 401-417 De Strooper B, Karran E. Cell 2016;164:603-615 Deane Ret al. J Clin Invest 2012;122:1377-1392 Giri Met al, Clin Interv Aging. 2016;11:665-81 Heneka MT et al. Lancet Neurol 2015;14:388405 Leng F, Edison P. Nat Rev Neurol 2021;17:157-