APOE4 carriers have a unique cerebrospinal fluid and plasma proteome signature irrespective of cognitive diagnosis

Our findings demonstrate that APOE4 carriage defines both the CSF and plasma proteome irrespective of cognitive status. First, this suggests that APOE4 carriers have systemic biological alterations. Second, our findings suggest that the underlying biological changes in APOE4 carriers are essential but not sufficient for developing MCI and AD. It may be the case that these biological changes make APOE4 carriers more vulnerable to environmental insults, such as viral infections, and together these factors drive MCI and AD pathogenesis.