Is apoE plasma level associated with MCI? Findings from the Framingham Heart Study

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Background: In-vitro studies suggest that the apoE3 isoform is associated with increased neuronal plasticity, reduced Aβ neurotoxicity, and prevention of NFT formation relative to the apoE4 isoform. It has been reported that high apoE3 levels are related to greater neuronal growth; whereas high apoE4 levels have been shown to inhibit neuronal growth. Whether apoE plasma levels can differentiate between those with and without MCI in APOE-ϵ3 and APOE-ϵ4 positive individuals has not been explored. Objective: To determine if apolipoprotein E (apoE) isoform plasma level is associated with mild cognitive impairment (MCI). Methods: In this cross-sectional study, 374 non-demented individuals (mean age= 72, SD= 4.4,range= 65-88) from the Framingham Heart Study were classified into MCI and non-MCI groups using the Petersen criteria of performance deficits of 1.5 SD below age and educated adjusted mean scores on memory (WAIS Logical Memory subtest) and non-memory tests (WAIS Similarities subtest, Trail-making test, Boston Naming Test, and the Hooper Visual Organization test). Four MCI categories were created: 1) Amnestic Single Domain MCI (impairment in memory only), 2) Amnestic Multiple Domain MCI (impairment in memory and one non-memory test) 3) Non-Amnestic Single Domain MCI (impairment on one non-memory test only), 4) Non-Amnestic Single Domain MCI (impairment on two or more non-memory measures). To assess the relationship between apoE isoform plasma level and MCI, individuals were divided into APOE-ϵ3 (ϵ3/ϵ3, n= 287) and APOE-ϵ4 (ϵ4/ϵ4, ϵ3/ϵ4, n= 87) genotype groups. Conclusions: There were no significant differences in age, education, gender, and body mass index (BMI) between individuals with and without MCI in either the APOE-ϵ3 and APOE-ϵ4 groups. Among APOE-ϵ3 individuals, an ANOVA, adjusted for age, education, and gender, revealed a significantly lower mean apoE3 plasma level in the Amnestic Single Domain MCI group (p= 0.05) compared to the non-MCI group (7.3 mg/dl and 10.3 mg/dl, respectively). There were no significant MCI group differences in apoE plasma level for APOE-ϵ4 positive individuals. These findings suggest that higher apoE3 levels may offer protection from age-related cognitive decline.