Novel IVD Tool for Rapid APOE Genotyping May Aid in Alzheimer Disease Risk Stratification

Author(s):

Key Takeaways

APO-Easy rapidly genotypes APOE variants, particularly the ε4 allele, aiding risk stratification and therapeutic decisions in Alzheimer's disease.
The assay uses real-time quantitative PCR with hydrolysis-probe technology for precise allelic discrimination, validated across multiple cohorts.
APOE4 is a major genetic risk factor for late-onset AD, accelerating disease onset and amyloid-β accumulation, influencing disease progression.
Research using iPSC-derived neurons and astrocytes explores APOE4's role in enhancing amyloid-β toxicity and neurodegeneration, informing targeted interventions.

A recent poster presentation at the 2025 AD/PD conference revealed that a novel assay could provide absolute allelic discrimination for APOE genotyping, supporting precision medicine in AD treatment.

Hüseyin Firat, MD, PhD

(Credit: Amoneta Diagnostics)

A recently developed in vitro diagnostic (IVD) tool, APO-Easy (Amoneta Diagnostics), has demonstrated the ability to rapidly genotype APOE variants, particularly the ε4 allele, a major genetic risk factor for Alzheimer disease (AD). The assay, designed to aid risk stratification and guide therapeutic decisions, meets CE and IVD certification standards.¹

Researchers developed a real-time quantitative polymerase chain reaction utilizing hydrolysis-probe technology to distinguish the rs429358 and rs7412 single nucleotide polymorphisms (SNPs) associated with APOE alleles. The test, optimized for use on the ThermoFisher QS5-Dx instrument, can enable precise allelic discrimination through FAM and VIC fluorophore detection.

Presented by lead author Hüseyin Firat, MD, PhD, president and chief scientific officer at Amoneta Diagnostics, at the 2025 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held April 1-5 in Vienna, Austria, the assay has undergone validation across multiple cohorts, confirming its ability to deliver absolute allelic discrimination in patient samples. By providing a rapid and reliable method for determining APOE genetic status, APO-Easy could align with the growing emphasis on precision medicine in AD care.

With 2 new antibody-based therapies targeting amyloid plaques now available, authors noted that APOE genotyping has become increasingly relevant. Studies have shown that patients carrying the ε4 allele are at heightened risk for amyloid-related imaging abnormalities, including edema and hemosiderin deposition, making genetic screening critical for treatment safety.²

Building on the need for precise APOE genotyping in AD management, recent research is further clarifying the role of APOE4 in disease progression. APOE4, the strongest genetic risk factor for late-onset AD, not only increases susceptibility but also accelerates disease onset and amyloid-β (Aβ) accumulation. New findings from a different study presented at AD/PD 2025 revealed that APOE directly co-aggregates with Aβ in the brain, potentially exacerbating neurotoxicity and influencing disease progression.²

To better understand the interplay between APOE isoforms and Aβ, researchers have developed induced pluripotent stem cell (iPSC)-derived cortical neurons expressing APOE3 and APOE4, cultured alongside astrocyte-derived APOE3 and APOE4. This system allows scientists to determine whether APOE4 specifically enhances Aβ toxicity or if neurons carrying high-risk APOE4 variants are inherently more susceptible to damage.

Using single-molecule and super-resolution imaging, investigators are analyzing the size, shape, and aggregation rates of Aβ-apoE complexes. In parallel, they are measuring neuronal health through markers such as Caspase-3/7 release, neurite retraction, synapse density, and electrophysiological activity, providing insight into how different APOE isoforms drive neurodegeneration.

This research aims to define the structure-function relationships of Aβ-APOE interactions, shedding light on why APOE4 carriers face a significantly increased risk of AD. As the field moves toward precision medicine, understanding these mechanisms could inform targeted interventions and therapeutic strategies for high-risk individuals.

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REFERENCES
1. Kocaefe Ç, Casanova M, Pham-Van L, et al. APO-EASY: A novel IVD tool for rapid APOE genotyping aiding towards risk stratification for Alzheimer's Disease. Presented at: 2025 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD); April 1-5. Vienna, Austria. Abstract 1829.
2. Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron. 2009;63(3):287-303. doi:10.1016/j.neuron.2009.06.026
3. Urbanek A, Garland EF, Prescott E, De S. APOE and Amyloid-Beta Interaction-Mediated Dysfunction in Alzheimer’s Disease. Presented at: 2025 International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD); April 1-5. Vienna, Austria. Abstract 1306.