Dementias of the Alzheimer Type: Views Through the Lens of Evolutionary Biology Suggest Amyloid-Driven Brain Aging Is Balanced Against Host Defense

Abstract

We propose that Alzheimer’s disease (AD) and related neurodegenerative conditions can be best understood within an evolutionary framework as a trade-off with host defense, with the apoE allele system as an example. This chapter reviews this hypothesis and evaluates the relevant evidence. We focus the “Darwinian lens” on two major features of human aging: First, inflammatory changes with mild amyloid deposits and modest synapse loss that arise in shorter lived species during aging; second, we contrast these mild changes with the more aggressive neurodegenerative changes of AD found only in humans. To some extent, mild AD-like changes arise at later ages in primate species with widely differing life spans from lines that diverged 50 or more million years ago. We discuss the changing role of host defense in modern human populations that are under greatly reduced natural selection from infectious agents.