Fig.1.

Schematic of the APN regulation of amyloiogenic evolvability and AD. According to EVH, Aβ is involved in evolvability against stressors in the extracellular spaces, while tau is against the stressors in the cytoplasm in parental brain. In response to multiple stressors, aggregation of APs, including Aβ and tau, is induced, and the resulting protofibrils of APs might confer the stress resistance. Subsequently, the APs protofibrils might be transmitted to off spring via germ cells. By virtue of the information carried by the transmission of APs protofibrils in reproduction, off spring can cope with the forth-coming stresses in the brain to escape from neurodevelopmental diseases. Thus, the APs protofibrils might be involved in evolvability against stressors in brain, which is evolutionally beneficial. However, the evolvability of APs protofibrils may increase the risk of AD through the antagonistic pleiotropy in aging. APN may be neuroprotective and stimulate evolvability by the APs protofibrils in reproduction. However, APN might stimulate the development of AD in aging, namely APN paradox. Therefore, decrease of APN expression could be therapeutic (Tx).