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

Abstract

Including apolipoprotein E-ε4 (APOE-ε4) status and older age into consideration may increase the accuracy of plasma Aβ42/Aβ40 detecting Aβ+ individuals, but the rationale behind this remains to be fully understood. Besides, both Aβ pathology and vascular diseases are related to neurodegeneration and cognitive decline, but it is still not fully understood how APOE-ε4 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 Aβ42/Aβ40 measured by liquid chromatography tandem mass spectrometry, and 18F-florbetapir Aβ PET as well as their prediction of longitudinal adjusted hippocampal volume (aHCV) and cognition in APOE-ε4 carriers and non-carriers. We found older age predicted faster WMH increase (p = 0.024) and cortical Aβ accumulation (p = 0.043) in APOE-ε4 non-carriers only, whereas lower plasma Aβ42/Aβ40 predicted faster cortical Aβ accumulation (p < 0.018) regardless of APOE-ε4 status. While larger WMH and underweight predicted (p < 0.05) faster decreases in aHCV and cognition in APOE-ε4 non-carriers, lower plasma Aβ42/Aβ40 predicted (p < 0.031) faster decreases in aHCV and cognition in APOE-ε4 carriers. Higher Aβ PET also predicted faster rates of aHCV (p = 0.010) in APOE-ε4 carriers only, but was related to faster rates of cognitive decline (p < 0.022) regardless of APOE-ε4 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-ε4 allele, which may help the design of anti-Alzheimer’s clinical trials.