Abstract
The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer’s disease (AD). We sought to investigate the distribution of APOE genotypes across the full clinical AD spectrum including AD, late-stage amnestic mild cognitive impairment (L-aMCI), early-stage aMCI (E-aMCI), subjective memory impairment (SMI), and controls. We prospectively recruited 713 AD patients, 735 aMCI patients, 575 SMI patients, and 8,260 individuals as controls. The frequency of the APOE e4 allele revealed an ordered fashion in the AD (30.8%), L-aMCI (24.0%), E-aMCI (15.1%), SMI (11.7%), and control (9.1%) groups. APOE e3/e4 and e4/e4 genotype frequencies also appeared in an ordered fashion in the AD group (39.1% of e3/e4 and 10.9% of e4/e4), as well as the L-aMCI (28.3% and 9.4%), E-aMCI (22.3% and 3.7%), SMI (18.3% and 1.9%), and control (15.1% and 0.8%) groups. In the comparisons of APOE e3/e3 vs. e3/e4 genotypes, all patient groups had a higher frequency of APOE e3/e4 relative to the control group. Relative to the SMI and E-aMCI groups, the AD and L-aMCI groups had higher frequency of the APOE e3/e4 genotype, and the AD group had a higher frequency relative to the L-aMCI group. However, there was no significant difference between the E-aMCI and SMI groups. In our longitudinal data, APOE e4 carrier showed a steeper incline slope in a clinical dementia rating sum of boxes (CDR-SB) score than APOE e4 non-carrier in SMI (B = 0.0066, p = 0.0104), E-aMCI (B = 0.0313, p < 0.0001), and L-aMCI (B = 0.0178, p = 0.0007). APOE e4 carrier showed a steeper decline slope in the CDR-SB than APOE e4 non-carrier in AD (B = − 0.0309, p = 0.0003). These findings suggest that E-aMCI and SMI are associated with a similarly increased frequency of the APOE e4 allele compared to controls, suggesting a greater genetic risk for AD and the importance of monitoring the allele more closely.
Highlights
The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer’s disease (AD)
Relative to the subjective memory impairment (SMI) and early-stage amnestic MCI (aMCI) (E-aMCI) groups, the AD and late-stage amnestic mild cognitive impairment (L-aMCI) groups had a higher frequency of the APOE e3/e4 genotype, while the AD group had a higher frequency relative to the L-aMCI group
Few studies have investigated the frequency of APOE e4 alleles in the continuum of normal controls in E-MCI (NC) and AD in Asia[7], some similar studies in Western countries have been reported[5,6]
Summary
The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer’s disease (AD). APOE e4 carrier showed a steeper decline slope in the CDR-SB than APOE e4 non-carrier in AD (B = − 0.0309, p = 0.0003) These findings suggest that E-aMCI and SMI are associated with a increased frequency of the APOE e4 allele compared to controls, suggesting a greater genetic risk for AD and the importance of monitoring the allele more closely. The aim of this study was to evaluate the distribution of the APOE e4 genotype in AD, L-aMCI, E-aMCI, SMI, and control groups in a relatively large cohort of patients across the full clinical AD spectrum, and to compare the frequency of the genotype between the different diagnostic categories. We determined whether APOE e4 genotype might affect clinical progression measured by a clinical dementia rating sum of boxes (CDRSB) score in AD, L-aMCI, E-aMCI, and SMI
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