Biomarkers.

Area of Science:

• Neurology
• Genetics
• Pharmacogenomics

Background:

• Recent approvals of anti-amyloid-beta (Aβ) antibody drugs for Alzheimer's Disease (AD) necessitate risk assessment for side effects.
• Amyloid-Related Imaging Abnormalities (ARIA) are common side effects, with incidence varying by apolipoprotein E (APOE) genotype.
• APOE genotyping is recommended prior to anti-Aβ therapy to identify ARIA risk.

Purpose of the Study:

• To confirm the utility of the APOE Genotyping Single Nucleotide Polymorphism (SNP) Array for assessing ARIA risk.
• To validate the APOE Alzheimer's Disease Risk LDT offered by Laboratory Corporation of America Holdings.

Main Methods:

• DNA samples from whole blood were analyzed using custom genotyping arrays.
• Two common APOE gene variants (rs429358 and rs7412) were assessed.
• Individuals were classified into six distinct APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4).

Main Results:

• The APOE Genotyping SNP Array demonstrated 100% concordance with the Polymerase Chain Reaction (PCR) method.
• The PCR method used was consistent with procedures from the Donanemab Phase III clinical trial (TRAILBLAZER-ALZ 2).
• High concordance was observed across all six tested APOE genotypes, with a minimum of six samples per genotype.

Conclusions:

• The APOE Genotyping SNP Array is a validated and valuable tool for predicting ARIA risk in patients undergoing anti-Aβ antibody treatment.
• Widespread adoption of this test is anticipated to improve patient safety and treatment selection for Alzheimer's Disease.
• This genetic test supports personalized medicine approaches in AD treatment by identifying patients at higher risk for ARIA.