Apolipoprotein E proteotyping as a valid alternative to genotyping in clinical practice

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• The apolipoprotein E ε4 (APOE ε4) allele is a significant risk factor for Alzheimer's disease.
• APOE ε4 status is crucial for managing amyloid-related imaging abnormalities during anti-amyloid therapy.
• Current APOE genotyping methods can be invasive or time-consuming.

Purpose of the Study:

• To evaluate plasma apolipoprotein E4 (ApoE4) levels as a diagnostic marker for APOE ε4 allele status.
• To compare the accuracy of plasma ApoE4 quantification with traditional APOE genotyping.
• To assess the utility of ApoE proteotyping in clinical settings.

Main Methods:

• Plasma samples from 70 participants were analyzed using Lumipulse®G Pan-ApoE and ApoE4 assays.
• ApoE4 concentrations and the ApoE4/Pan-ApoE ratio were calculated.
• Results were compared with established APOE genotyping data.

Main Results:

• Significant differences in ApoE4 concentrations and the ApoE4/Pan-ApoE ratio were observed across APOE ε4, ε3/ε4, and ε4/ε4 genotype groups.
• No correlation was found between plasma ApoE4 levels and age, sex, creatinine, or AD cerebrospinal fluid biomarkers.
• The proteotyping method demonstrated excellent diagnostic performance for classifying APOE haplotypes.

Conclusions:

• Plasma ApoE4 quantification is a highly accurate method for determining APOE ε4 allele status.
• ApoE proteotyping offers a non-invasive and effective alternative to genetic testing.
• This approach can aid in patient stratification for Alzheimer's disease therapies.