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AD/PD 2022 | Inflammation in Alzheimer’s disease and the potential of GM-CSF treatment

The role of inflammation in Alzheimer’s was first identified by Alois Alzheimer after observing activated astrocytes and microglia in the brains of patients. Still, the correlation between inflammation and Alzheimer’s disease is not proven to be causative and to date, studies aiming to reduce inflammation have failed to improve patient cognition. One of the clearest clinical indications that inflammation is involved in Alzheimer’s pathogenesis is the finding that patients with rheumatoid arthritis tend not to develop Alzheimer’s, showing three-to-eight-fold protection. Huntington Potter, PhD, University of Colorado School of Medicine, Aurora, CO, explains the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by patients with rheumatoid arthritis results in protection against Alzheimer’s disease. Treating mouse models with GM-CSF resulted in normalized cognition and a 60% reduction in amyloid deposits. A Phase II, double blind, placebo trial of GM-CSF in patients with mild to moderate Alzheimer’s disease (NCT01409915) led to cognitive improvement and improvement in three major biomarkers of Alzheimer’s disease: amyloid, tau and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), after three weeks of treatment. Prof. Potter mentions funding a new 24-week trial (NCT04902703) which will use blood biomarkers, cognition tests, and brain imaging to further test GM-CSF treatment in patients with Alzheimer’s disease. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.