Genomics of Alzheimer’s disease

Pathogenesis of Alzheimer’s disease (AD) is impacted by a combination of genetic risk factors. A large number of genetic variants associated with AD exhibit protective or damaging effects that influence the progression of the disease. The genotype-phenotype relationship is often illustrated by causal genetic mutations/risk variants and their corresponding alterations in the metabolism of amyloid β protein (Aβ). Interactions among these genetic risk factors and their impact on vascular function emerge to be critical processes for drug development and adverse effect management. This chapter will primarily focus on Aβ as a target corresponding to genetic variants and showcase important Aβ-based approaches in therapeutic application of Food and Drug Administration-approved Aβ-monoclonal antibodies for the treatment of AD. The development of a DNA Aβ42 trimer vaccine as potential therapy for AD is emphasized in the section on immunotherapeutics.