Association of apolipoprotein E in peripheral blood and in vivo Alzheimer’s disease pathologies in nondemented older adults

Abstract

AbstractBackgroundPrevious studies reported the link between apolipoprotein E (apoE) in peripheral blood and risk of Alzheimer’s disease (AD) dementia. However, underlying mechanism for this link remains unclear. We investigated whether serum apoE concentration is associated with in vivo AD pathologies in nondemented older adults.MethodA total 437 nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. All participants underwent comprehensive evaluation including clinical assessment, blood sampling, as well as 11C‐PiB PET and MRI. A subset of participants (N=130) also underwent 18F‐AV1451 PET for measurement of brain tau pathologies. All participants were divided into low, middle, and high apoE concentration tertile groups (i.e., T1, T2, and T3).ResultThere were no significant differences in demographic and clinical variables except the frequency of female and rate of apoE ε4 allele (APOE4) positivity; the lower serum apoE was associated with fewer female (40.1%, 61.6%, and 67.8% for T1, T2, and T3, respectively) and higher APOE4 positivity rate (34.3%, 25.2%, and 16.8%). In terms of AD biomarker, Aβ positivity rate showed significant negative association with serum apoE (40.1%, 31.8%, and 24.8%), which remained significant after adjustment of covariates including age, sex, and diagnosis. In addition, reduced AD‐signature region volume, a neurodegeneration biomarker of AD, was significantly associated with lower serum apoE after controlling the same covariates. With regard to tau biomarker, positivity rate of global tau deposition showed significant negative association with serum apoE level (56.8%, 50%, and 20%) after adjustment of covariates. When we additively controlled the effect of APOE4 positivity, the associations between low serum apoE and greater neurodegeneration and tau positivity remained significant, whereas the association between apoE and Aβ positivity did not reach statistical significance.ConclusionIn the present study, low serum apoE was associated with greater burden of in vivo AD pathologies and such association appears even independent of APOE4 carrier status in regard of tau deposition and neurodegeneration. The finding suggests a potential role of serum apoE as a surrogate marker for in vivo AD pathologies in nondemented older adults.