Effect of APOE 4 Allele on Levels of Apolipoproteins E, J, and D, and Redox Signature In Circulating Extracellular Vesicles from Cognitively Impaired with No Dementia Participants Converted to Alzheimer's Disease

Introduction The substantial link between apolipoprotein E (APOE) epsilon 4 allele and oxidative stress may underlie enhanced Alzheimer's disease (AD) risk. Here, we studied the impact of APOE epsilon 4 on the level of apolipoproteins with antioxidant activities along with oxidative markers in circulating extracellular vesicles (cEVs) and plasma from cognitively impaired-not demented (CIND) individuals converted to AD (CIND-AD). Methods Apolipoproteins E, J, and D and antioxidant response markers were determined in cEVs and plasma using immunoblotting, electrochemical examination, and spectrofluorimetry. Results Total antioxidant capacity and apolipoprotein D levels in cEVs, as judged by regression analysis and cognitive performance correlations, allowed us to differentiate CIND APOE epsilon 4 carriers from controls and to predict their progression to AD 5 years later. Discussion Our findings support the pathological redox linkage between APOE epsilon 4 and AD onset and suggest the use of cEVs oxidative signature in early AD diagnosis.