Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment

• Published in: Scientific reports 2020-08, Vol.10 (1), p.13365-13365, Article 13365
• Main Authors: Cho, Hanna, Kim, Young-Eun, Chae, Wonjeong, Kim, Ko Woon, Kim, Jong-Won, Kim, Hee Jin, Na, Duk L., Ki, Chang-Seok, Seo, Sang Won
• Format: Article
• Language: English
• Subjects: 692/499; 692/617/375/132/1283; Aged; Alleles; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Apolipoprotein E4; Apolipoprotein E4 - genetics; Apolipoprotein E4 - metabolism; Apolipoproteins; Case-Control Studies; Cognitive ability; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Dementia disorders; Female; Gene Frequency - genetics; Genetic diversity; Genotype; Genotypes; Humanities and Social Sciences; Humans; Male; Memory; Memory Disorders - genetics; Memory Disorders - metabolism; Middle Aged; multidisciplinary; Neurodegenerative diseases; Neuropsychological Tests; Prospective Studies; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-69603-w

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