Apolipoprotein E genotypes and plasma levels in mild cognitive impairment conversion to Alzheimer's disease: A follow‐up study

Abstract

Mild cognitive impairment (MCI) is the transition stage between the normal aging process and dementia itself. The most common clinical phenotype is amnestic MCI (aMCI) [subtypes: single domain (sMCI) and multiple domains (mMCI)], which is considered prodromal to Alzheimer's disease (AD). The APOE (apolipoprotein E) e4 allele is the most important genetic risk factor for AD, but its association with MCI onset and conversion to AD is controversial. In this follow-up study of 88 aMCI patients (68% sMCI and 32% mMCI at baseline), we examined APOE genotypes and plasma levels in relation to MCI development and progression based on their clinical/cognitive data obtained at baseline and follow-up assessment (mean follow-up time = 6.6 ± 3.4 years). A control sample (n = 164) was collected in previous investigations. The overall conversion rate to mMCI or AD was 52.2%. The APOE e4 allele was associated with a higher risk of developing MCI (OR: 2.23; 95%CI: 1.22-4.08). The conversion rate in the e4 allele carriers (32% of the sample) was 71%, and the e4 allele was associated with a higher risk of conversion to mMCI/AD (OR: 4.1; 95%CI: 1.2-13.6). APOE e2 allele carriers were 7% (all sMCI) and none progressed to mMCI/AD. Among MCI subjects, e4 carriers had the lowest plasma apoE levels (37.8 ± 12.5 mg/L), and e2 carriers had the highest (78.6 ± 38.1 mg/L). APOE e4 is a risk allele for the development and progression of aMCI, the APOE e2 allele seems to be protective, and apoE levels associated to them are an integral part of their action. © 2016 Wiley Periodicals, Inc.

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer’s Disease

“…For instance, previous studies have reported that levels of apoE protein are decreased in APOE4 compared to APOE3 mice (for both APOE-TR and EFAD mice) and in individuals who are carriers of the APOE ε4 allele compared to non-carriers [20, 36, 37]. In particular, studies have shown that plasma apoE levels are much lower among ε4 homozygous MCI subjects who convert to AD [38]. These studies support further examination of systemic AA and DHA imbalance in relation to the APOE genotypes and their contribution to AD pathology.…”

The effect of APOE genotype on Alzheimer's disease risk is influenced by sex and docosahexaenoic acid status

“…Such associations are also apparent in mild cognitive impairment (MCI). APOE-ε4 carriers are 3.0-3.7 times more likely to develop MCI compared to all other groups (Viticchi et al, 2017) and APOE-ε4 MCI are more likely to convert to a more severe state of MCI (mMCI) or AD (Scarabino et al, 2016). APOE-ε4 has been associated with hippocampal, amygdala and medial-temporal lobe atrophy (Lupton et al, 2016;Manning et al, 2014), which underlies the greater development and conversion rates in this genotype subgroup.…”

The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study

“…Patients with MCI have an annual conversion rate to AD of 10–15%, in contrast to only 1–2% among healthy individuals (Bruscoli and Lovestone, 2004; Chen et al, 2017; Petersen et al, 2001, 1999). The presence of the ApoE ε4 allele increases the odds of converting from amnestic MCI to ADD by 4.1 fold (95% CI: 1.2–13.6) (Petersen et al, 2005; Scarabino et al, 2016). Yet in spite of these findings, little is known about how the presence of the ApoE ε4 allele induces pathological changes in the context of MCI.…”