CLU and Alzheimer disease: The regulatory mechanism of Clu in regard to the BBB in AD is complex and involves multiple pathways, including: (1) through its interaction with Aβ, Clu is able to bind to Aβ and mediate Aβ clearance by interacting with low-density lipoprotein-related protein 2 (LRP2), myeloid cell trigger receptor 2 (TREM2), or heparan sulfate (HS).