HAI Book 2025 - Flipbook - Page 124
Colón-Badillo, Vanessa
11
Targeted plasma eQTL and pQTL to identify potential novel biomarker
for Alzheimer's disease in African Americans
Vanessa M. Colón-Badillo1, Joseph S. Reddy2, Jiangli Jin1, Sarah J. Lincoln1, Charlotte C. G.
Ho1, Julia E. Crook2, Xue Wang2, Kimberly G. Malphrus1, Thuy Nguyen1, Jean Marrero-Polanco1,
Nikoleta Tamvaka1, John A. Lucas3, Neill R. Graff-Radford3, Nilüfer Ertekin-Taner1,3, Minerva
M. Carrasquillo1
1
Mayo Clinic, Department of Neuroscience, Jacksonville, FL, US
Mayo Clinic, Department of Quantitative Health Sciences, Jacksonville, FL, US
3
Mayo Clinic, Department of Neurology, Jacksonville, FL, US
2
Given the overlap of symptoms between Alzheimer9s disease (AD) and other dementias, it is essential to develop
widely accessible biomarkers that will ensure an accurate diagnosis to enable its proper treatment. African
Americans (AA) are 2x more likely to develop AD than non-Hispanic whites, and yet they remain underrepresented
in AD research. The few studies conducted in AA suggest that there are different factors that influence AD in this
population; therefore, it is possible that different biomarkers and/or therapies may be needed to effectively treat
AD in AA. In this study, we aimed to determine if genetic variants that show association in AA with AD-risk, plasma
transcript and/or protein levels, may serve as accurate and accessible AD biomarkers.
In 189 clinically-diagnosed AA AD cases and 183 AA cognitively unimpaired (CU) controls, we performed targeted
DNA sequencing of 10 AD-associated loci. Genetic variants were tested for association with plasma transcripts
and total tau protein levels previously measured in this cohort using a nanoString custom panel and Simoa assays,
respectively. In receiver operating characteristic (ROC) analyses, the most significant e/pQTLs were added
sequentially to a base model that included only age and sex to identify e/pQTL that improved the accuracy to
correctly classify AD cases vs. CU.
Of the 5,112 variants identified in the targeted sequencing, 70 were nominally associated with plasma
transcript/protein levels and with AD-risk. ROC analysis of age, sex, e/pQTL in APOE, SORL1, TLR4, EPHA1, ABCA7,
CLU, and CR1, and plasma levels of APP, ABCA7, AKAP9, CD14, CLU, and APOE-ɛ4 dosage achieved 88.2% area under
the curve to discriminate AD vs. CU, a 30.4% improvement over a model that only included age and sex.
Plasma transcript levels and e/pQTLs are promising diagnostic biomarkers for AD that may improve accessibility
and reduce costs for a more accurate diagnosis of AD.
Keywords: blood biomarkers, eQTL, pQTL, African Americans, Alzheimer’s Disease
HAI2025 - 124
