CLU and Alzheimer disease: Key issues that could be addressed to provide further insight are: (1) the relationship between copper, cholesterol and tau; (2) whether the major risk associated factors ApoE and ApoJ are associated with copper in vivo and whether copper is necessary for their function; (3) whether copper is associated with HDL-like particles containing cholesterol-bound ApoE and if so, the functional significance of this in both copper and cholesterol transport and AD.