Apolipoprotein E genotypes and plasma levels in mild cognitive impairment conversion to Alzheimer's disease: A
Daniela Scarabino1, Elisabetta Broggio2, Giuseppe Gambina2
1CNR Institute of Cellular Biology and Neurobiology, Monterotondo Scalo, Rome, Italy.
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.
Insights
The APOE e4 allele increases the risk of developing and progressing amnestic mild cognitive impairment (aMCI). Conversely, the APOE e2 allele appears protective against aMCI progression.
Area of Science:
- Neuroscience
- Genetics
- Gerontology
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.
- Amnestic MCI (aMCI) is the most common subtype and a potential prodrome to Alzheimer's disease (AD).
- The role of the apolipoprotein E (APOE) e4 allele in MCI development and progression remains debated.
Purpose of the Study:
- To investigate the association of APOE genotypes and plasma apoE levels with the development and progression of aMCI.
- To examine the impact of APOE e4 and e2 alleles on MCI conversion rates and cognitive decline.
Main Methods:
- Follow-up study of 88 aMCI patients with assessment of APOE genotypes and plasma apoE levels.
- Clinical and cognitive data collected at baseline and during a mean 6.6-year follow-up.
- Comparison with a control sample (n=164) from previous studies.
Main Results:
- The overall conversion rate from MCI to mMCI or AD was 52.2%.
- APOE e4 allele carriers showed a higher risk of developing MCI (OR: 2.23) and converting to mMCI/AD (OR: 4.1).
- APOE e2 allele carriers (all sMCI) did not progress to mMCI/AD, suggesting a protective effect. Lower plasma apoE levels were observed in e4 carriers, while e2 carriers had higher levels.
Conclusions:
- The APOE e4 allele is a significant risk factor for the development and progression of aMCI.
- The APOE e2 allele may offer protection against aMCI progression.
- Plasma apoE levels are associated with APOE genotypes and may mediate their effects on aMCI.
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