4,068 posters, 219 videos, 101 topics, 69 sessions, 14,365 authors, 6,128 institutions

Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

5916

Plasma APOE4 Proteotyping Enables Accurate Carrier Classification And Reveals Molecular Links To Alzheimer’s Risk

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Poster Presenter

Lamia Choity

Authors

Lamia Choity, Ruyu Shi, Marissa Farinas, Xuemei Zeng, James Emanuel, Anum Saeed, Steven Reis, Oscar Lopez, Ann Cohen, Ariel Gildengers, Kristine Wilckens, Thomas Karikari

Affiliations

University of Pittsburgh, University of Pittsburgh School of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh

Part of Topic

Plasma APOE4 Proteotyping Enables Accurate Carrier Classification And Reveals Molecular Links To Alzheimer’s Risk:

Lamia T. Choity¹, Ruyu Shi¹, Marissa F. Farinas¹, Xuemei Zeng¹, James E. Emanuel, B.S.¹, Anum Saeed¹^,2, Steven E. Reis, Prof¹^,2, Oscar L. Lopez¹^,2, Ann D. Cohen², Ariel G. Gildengers¹^,2, Kristine A. Wilckens¹^,2, Thomas K. Karikari¹^,2.
¹University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, ²University of Pittsburgh, Pittsburgh, PA, USA.

Key Message: APOE4 proteotyping captures genotype-level risk and becomes most useful when embedded in a multiplex AD plasma biomarker panel.

Background:

•APOE ε4 is the strongest genetic risk factor for late-onset AD and confers dose-dependent amyloid risk.

•APOE status is usually determined by DNA genotyping, but plasma proteotyping can measure APOE4-specific protein signal in the same blood-based workflow as other AD biomarkers

•This makes APOE4 proteotyping attractive for scalable risk assessment and mechanistic biomarker profiling

Methods:

•Participants

Multi-cohort (ADRC, ALPS, LATTICE, and HeartSCORE) plasma obtained from 1,658 individuals

•Paired measurements

Plasma NULISAseq CNS panel + TaqMan APOE genotyping

•Carrier classification

ROC/Youden thresholds for carrier status and ε4 copy number

•Clinical relevance

Amyloid positivity + CDR-SB decline models in ADRC

•Multiplex planel

APOE4 + pTau-217 + GFAP + NfL vs genotype alone
Results:

Carrier status: adjusted AUC 0.978; external validation shows no observed carrier misclassifications across ALPS, HeartSCORE, and LATTICE. Gene-dose threshold separates heterozygous vs homozygous carriers.

The full NULISA panel outperforms genotype alone for amyloid prediction (AUC 0.920 vs 0.764). Adding genotype back does not meaningfully improve performance.

Differential abundance supports molecular links between APOE4 carrier status and AD-relevant plasma markers, including tau/GFAP-related signals.
Conclusion:

•Plasma APOE4 is a strong blood-based surrogate for APOE ε4 genotyping

•Its main value appears to be genotype-level risk capture, not fine-grained risk stratification within established carriers

•A multiplex plasma panel provides more amyloid-risk information than genotype alone.

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