Importantly, in human CSF, oAβ increased and was greater with APOE4 in the AD cohort, in contrast to total Aβ42 levels that decrease with AD compared to NAD, with levels at the limit of detection in the AD cohort with both APOE3 and APOE4. Taken together, the low levels of soluble apoE4/Aβ complex and high levels of soluble oAβ suggest a potential basis for APOE4-induced AD risk. Here, APOE is linked to Alzheimer disease.