Title:  A unified theory for Alzheimer’s disease and beyond

　　Speaker: Yelin Chen Ph.D.

　　Time: 10:00-11:30 A.M., Wednesday, May 17th, 2023

　　Venue: Youcai Deng Hall, School of Life Sciences

　　Host:  Dr. Yan Song

　　Postdoc host: Dr. Zhaofa Wu

　　Abstract

　　The evidence supporting the causal role of Aβ in Alzheimer’s disease (AD) mainly come from the study of the rare form of familial AD (fAD). However, the role of Aβ in Alzheimer’s disease (AD) has been questioned due to the unsatisfying Aβ-targeting efforts in treating the much more common form of sporadic AD (sAD). Inevitably, this also challenges many fundamental understandings of AD itself. For example, although it remains clear that dysfunction in APP (Aβ precursor protein) γ-cleavage underlies fAD, whether sAD could be classified fundamentally as the same type of disease as fAD becomes widely questioned. We find that Apolipoprotein E (ApoE), the most important genetic risk factor of sAD, inhibits γ-secretase with a potency rank order inversely correlating to the AD risks that different ApoE isoforms impose, suggesting that the inhibition of γ-secretase by ApoE protects against the risk of sAD. Therefore, we identify misregulation of APP γ-cleavage as the shared mechanism underlying both forms of AD. In addition, we also present ApoE CT as a unique type of γ-inhibitor to treat AD.