APOE and Alzheimer disease: CLU is now considered the third greatest genetic risk factor for LOAD, after APOE and BIN1. From histopathological to biomarker studies, numerous lines of evidence also suggest a link between clusterin and AD, such as the observation that clusterin is upregulated in the hippocampus and cortex of the AD brain, colocalizing with amyloid beta (Aβ) plaques (May et al., 1990).