Reconsideration of Alzheimer’s Disease Therapy from a Viewpoint of Amyloidogenic Evolvability

 Presuming that Alzheimer’s disease (AD) might represent an antagonistic pleiotropic phenomenon derived from the evolvability of multiple amyloidogenic proteins, targeting such proteins simultaneously could enhance therapeutic efficacy. Furthermore, considering that amyloid-β (Aβ) immunotherapies during reproductive life stage might adversely decrease Aβ evolvability in an offspring’s brain, the disease-modifying Aβ immunotherapies should be limited to post-reproductive time in lifespan. Thus, current Aβ immunotherapy strategies should be revised accordingly. Given that the “adiponectin paradox” might underlie both amyloidosis and cognitive dysfunction in aging brain, blocking activin signaling situated downstream of the adiponectin paradox might be an alternative strategy to prevent AD.