Amyloid Immunotherapies for Alzheimer's disease

Alzheimer's Disease is the leading cause of dementia and a growing public health concern globally as people live longer. Until recently therapies for those affected by the disease have only been symptomatic with a modest effect at best. However, in the past year immunotherapy against amyloid-beta for AD had its first 2 successes in phase 3 clinical trials. However, despite statistically significant benefits to cognition, patients still continue to decline. Remarkably, the mechanism(s) for the beneficial effect of immunotherapy against amyloid-beta remain unclear. Evidence supports that antibodies induce the degradation of amyloid plaques by glial cells in the brain, but the relative importance of this plaque reduction to cognitive benefits is uncertain. In fact, amyloid plaques have increasingly not been viewed as the most toxic entity in the disease. Rather, experimental work has increasingly focused on soluble oligomeric species of amyloid-beta as linking with brain damage in AD. This thesis will explore the cellular mechanisms and effects of anti-amyloid immunotherapy in cellular and mouse models of Alzheimer's disease as well as their effects on cerebrospinal fluid and blood biomarkers.