Conversion from MCI to AD in patients with the APOE ε4 genotype: Prediction by plasma HCY and serum BDNF
Lei Zheng1, Xiangjun Kong2, Yongjian Cui3
1Central Laboratory, Harrison International Peace Hospital, Hengshui, Hebei, China.
Abstract:
Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease (AD). Possession of the apolipoprotein E (APOE) ε4 genotype is a major predictor of progression to AD, particularly in patients with aMCI. However, the use of APOE genotyping in the diagnosis of aMCI that evolves into AD is limited due to its low sensitivity and specificity. In this study, we found that there was a notable increase in plasma homocysteine (HCY) and significant decrease in serum brain-derived neurotrophic factor (BDNF) in aMCI that converts to AD in patients with the APOE ε4 allele. Both plasma HCY and serum BDNF had higher positive predictive values and were more sensitive biomarkers of aMCI. Additionally, a testing strategy employing plasma HCY and serum BDNF revealed increases in sensitivity, specificity, and predictive ability compared with the use of either biomarker alone. The present study demonstrates that MCI that evolves into AD in patients with the APOE ε4 genotype may be predicted by plasma HCY and serum BDNF.
Insights
Apolipoprotein E (APOE) ε4 carriers with amnestic mild cognitive impairment (aMCI) progressing to Alzheimer's disease (AD) show increased plasma homocysteine (HCY) and decreased serum brain-derived neurotrophic factor (BDNF). These biomarkers can predict progression to AD in aMCI patients.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Amnestic mild cognitive impairment (aMCI) represents a preclinical stage of Alzheimer's disease (AD).
- The apolipoprotein E (APOE) ε4 genotype is a significant risk factor for AD progression, especially in aMCI patients.
- Current diagnostic utility of APOE genotyping for predicting aMCI to AD conversion is limited by suboptimal sensitivity and specificity.
Purpose of the Study:
- To investigate novel plasma and serum biomarkers for predicting the conversion of aMCI to AD in APOE ε4 carriers.
- To evaluate the diagnostic and predictive performance of homocysteine (HCY) and brain-derived neurotrophic factor (BDNF) in this patient cohort.
Main Methods:
- Analysis of plasma homocysteine (HCY) levels and serum brain-derived neurotrophic factor (BDNF) concentrations in aMCI patients with and without APOE ε4 allele.
- Assessment of HCY and BDNF as potential biomarkers for predicting progression to AD.
- Evaluation of a combined testing strategy using both HCY and BDNF.
Main Results:
- A significant increase in plasma HCY and a significant decrease in serum BDNF were observed in aMCI patients with the APOE ε4 allele who converted to AD.
- Both plasma HCY and serum BDNF demonstrated higher positive predictive values and enhanced sensitivity as biomarkers for aMCI progression.
- A combined testing strategy incorporating plasma HCY and serum BDNF significantly improved sensitivity, specificity, and overall predictive accuracy compared to individual biomarkers.
Conclusions:
- Plasma HCY and serum BDNF are promising biomarkers for predicting the conversion of aMCI to AD in individuals carrying the APOE ε4 genotype.
- These biomarkers offer improved diagnostic and prognostic value over APOE genotyping alone for identifying at-risk individuals.
- The findings support the potential clinical utility of HCY and BDNF measurements in managing patients with aMCI and APOE ε4.
More Related Videos
06:23The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
07:26High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
Published on: July 18, 2017
Related Concept Videos
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:22Alzheimer's Disease: Treatment
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase