Effect of APOE ε4 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) ε4 allele and oxidative stress may underlie enhanced Alzheimer's disease (AD) risk. Here, we studied the impact of APOE ε4 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 ε4 carriers from controls and to predict their progression to AD 5 years later. DISCUSSION: Our findings support the pathological redox linkage between APOE ε4 and AD onset and suggest the use of cEVs oxidative signature in early AD diagnosis.