APOE-ε4 modulates the association among plasma Aβ42/Aβ40, vascular diseases, neurodegeneration and cognitive decline in non-demented elderly adults

Including apolipoprotein E-epsilon 4 (APOE-epsilon 4) status and older age into consideration may increase the accuracy of plasma A beta(42)/A beta(40) detecting A beta+ individuals, but the rationale behind this remains to be fully understood. Besides, both A beta pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-epsilon 4 modulates these relationships. In this study, we examined 241 non-demented Alzheimer's Disease Neuroimaging Initiative participants to investigate the associations among age, white matter hyperintensities (WMH), hypertension, hyperlipidemia, body mass index (BMI), plasma A beta(42)/A beta(40) measured by liquid chromatography tandem mass spectrometry, and F-18-florbetapir A beta PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-epsilon 4 carriers and non-carriers. We found older age predicted faster WMH increase (p = 0.024) and cortical A beta accumulation (p = 0.043) in APOE-epsilon 4 non-carriers only, whereas lower plasma A beta(42)/A beta(40) predicted faster cortical A beta accumulation (p < 0.018) regardless of APOE-epsilon 4 status. While larger WMH and underweight predicted (p < 0.05) faster decreases in aHCV and cognition in APOE-epsilon 4 non-carriers, lower plasma A beta(42)/A beta(40) predicted (p < 0.031) faster decreases in aHCV and cognition in APOE-epsilon 4 carriers. Higher A beta PET also predicted faster rates of aHCV (p = 0.010) in APOE-epsilon 4 carriers only, but was related to faster rates of cognitive decline (p < 0.022) regardless of APOE-epsilon 4 status. These findings may provide novel insights into understanding different mechanisms underlie neurodegeneration and cognitive decline in non-demented elderly adults with and without APOE-epsilon 4 allele, which may help the design of anti-Alzheimer's clinical trials.