New insights into innate immunity in Alzheimer’s disease: from APOE protective variants to therapies

Recent discoveries of rare variants of human APOE may shed light on novel therapeutic strategies for Alzheimer's disease (AD). Here, we highlight the newly identified protective variant [APOE3 Christchurch (APOE3ch, R136S)] as an example. We summarize human AD and mouse amyloidosis and tauopathy studies from the past 5 years that have been associated with this R136S variant. We also propose a potential mechanism for how this point mutation might lead to protection against AD pathology, from the molecular level, to cells, to mouse models, and potentially, to humans. Lastly, we extend our discussion of the recent insights gained regarding different APOE variants to putative therapeutic approaches in AD.