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Determining Accuracy of oAb as a Mechanistic Biomarker for Alzheimer's Disease in Human Plasma
Author(s) -
Faulk Naomi,
ValenciaOlvera Ana,
Collins Nicole,
LaDu Mary Jo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb159
Subject(s) - biomarker , disease , medicine , population , apolipoprotein e , oncology , genotype , risk factor , bioinformatics , biology , genetics , environmental health , gene
Alzheimer's disease (AD) is a fatal neurodegenerative disease that is the 6 th leading cause of death in the United States with no cure and few palliative treatments. Currently, there is no preventative treatment, and even if such a therapeutic could be identified, without a predictive biomarker, a target population for treatment could not be determined. Although the mechanism remains unclear, AD is caused by increased levels of the amyloid‐b peptide (Ab), which aggregates to form both amyloid plaques and soluble oligomeric Ab (oAb), the latter considered a proximal neurotoxin. We believe that levels of oAb in human plasma are a prognostic biomarker, and have developed and licensed a method for their detection (LOD <5pMol). While age is the greatest risk factor for AD, APOE4 is the greatest genetic risk factor, increasing risk up to 15‐fold compared to the more common APOE3 . Importantly, female (♀) APOE4 carriers have an increased risk for AD compared to male (♂) APOE4 carriers. Key to the success of this project has been the stratification of both control and AD subjects by sex within APOE genotype, with the results that plasma oAb levels are: ♀ APOE4 > ♂ APOE4 > ♀ APOE3 > ♂ APOE3 . This response was observed in two large human post‐mortem cohorts. However, stratification, the principle of personalized medicine, is simply not applied to AD populations. We now seek to threshold oAb levels using longitudinal and human AD trial data to establish prognostic potential, with the goal of partnering with the private sector for commercialization. Support or Funding Information LaDu lab funding includes an Anonymous Donor, the University of Illinois College of Medicine, and UIC Honors College Grant. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .