Biomarkers

Area of Science:

• Biochemistry
• Genetics
• Neuroscience

Background:

• The Apolipoprotein E (APOE) gene, particularly the ε4 allele, is a significant risk factor for Alzheimer's disease (AD).
• Homozygous APOE ε4/ε4 genotype increases the risk of adverse events during amyloid-lowering therapies.
• APOE genotyping is the current standard for determining ApoE4 zygosity, but proteotype assays offer potential advantages.

Purpose of the Study:

• To compare the performance of two automated ApoE4 proteotype immunoassays against traditional APOE genotyping.
• To evaluate the accuracy and efficiency of these novel assays for ApoE4 zygosity assessment.

Main Methods:

• Sixty-five EDTA-plasma samples were analyzed using the Beckman Coulter APOE ε4 RUO assay and the Fujirebio Lumipulse G ApoE4 and Pan-ApoE RUO assays.
• Assay results were compared against APOE PCR-based genotyping data.
• Manufacturer-provided cut-points were used to classify samples into no E4, heterozygous E4, and homozygous E4 categories.

Main Results:

• The Beckman Coulter assay achieved 100% accuracy in classifying ApoE4 zygosity across 65 samples.
• The Lumipulse G assay demonstrated 94% accuracy in classifying ApoE4 zygosity.
• APOE genotype distributions included ε3ε4 (46%), ε3ε3 (28%), and ε4ε4 (18%).

Conclusions:

• ApoE4 proteotype immunoassays offer a simplified and potentially more accessible method for assessing ApoE4 zygosity.
• These assays could serve as valuable alternatives to genotyping for individuals undergoing evaluation for amyloid-lowering treatments.