Low Plasma ApoE Levels Are Associated with Smaller Hippocampal Size in the Alzheimer's Disease Neuroimaging Initiative Cohort

Abstract

Apolipoprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here, we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer's Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE ε4 allele and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals.

Age, APOE and sex: Triad of risk of Alzheimer’s disease

“…Low plasma apoE is associated with a decrease in hippocampal volume, and shows less of a sex difference in concentration levels in ɛ4 individuals than between the other genotypes (179). However, normal ɛ4 men show greater AD-pathology and worse memory performance than normal ɛ4 women, pointing to an earlier incidence of vulnerability (127).…”

Toward more predictive genetic mouse models of Alzheimer's disease

“…In human brains, APOE is normally synthesized and secreted by astrocytes and microglia and binds to high-density lipoproteins to facilitate cholesterol and phospholipid transport to LDL receptors. Low plasma APOE and APOE4 genotype are associated with morphological changes to the hippocampus, specifically reductions in size [16, 17]. Mouse models for studying both Apoe function and the human APOE variants have been created and have highlighted a complex role for APOE in the aging and diseased brain.…”

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

“…Comparing to ApoE ε3, the ApoE ε4 isoform is more susceptible to proteolysis, leading to the accumulation of reactive fragments of ApoE ε4 in the cytosol, which results in cytoskeleton damage and neurodegeneration [8,9]. Teng et al [10] demonstrated that low plasma ApoE levels are significantly correlated with a smaller hippocampal size in patients with normal recognition or cognitive impairment. The authors claim that the plasma ApoE level may represent a peripheral marker of underlying AD in nondemented elderly individuals [10].…”

“…Teng et al [10] demonstrated that low plasma ApoE levels are significantly correlated with a smaller hippocampal size in patients with normal recognition or cognitive impairment. The authors claim that the plasma ApoE level may represent a peripheral marker of underlying AD in nondemented elderly individuals [10]. Many studies proved a contribution of APOE ε4 in the extracellular deposition of β-amyloid (Aβ), being a hallmark of AD.…”