Immunotherapeutic approaches against amyloid-β in drug discovery for alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The major pathological hallmark and culprit of AD is aggregation of the amyloid-β (Aβ) peptide. Since the Aβ abnormality begins in the asymptomatic stage of AD, immunotherapeutic approaches clearing Aβ aggregates are investigated as the most promising treatment in clinical trials. Both active and passive immunization against Aβ showed significant reduction of Aβ levels in the brain and enhancement of learning and memory. Albeit pathologically effective, these immunotherapeutic vaccines need to overcome side effects such as vasogenic edema and microhemorrhages. In this chapter, we introduce the basic concept of immunotherapy for clearance of Aβ, compare putative immunotherapeutic vaccine candidates, and discuss their benefits, disadvantages, and challenges.