Proteomic Profiles of Tau Positivity among an Ethnically Diverse Cohort: An HABS-HD Study

Purpose: PET tau has been well documented to precede Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). In the pursuit of increasing the accessibility of AD diagnosis, studies have shown that blood biomarkers including ptau181 trend with PET tau in Non-Hispanic Whites (NHW). Current literature shows limited studies on Mexican Americans (MA) who have a higher risk of AD at earlier ages. MA populations have shown to have significantly higher burden of blood biomarkers/metabolic markers that are associated with MCI including ptau181, insulin, and glucagon, but lower in plasma amyloid. Our aim is to look at the utility of AT(N) (amyloid, tau, neurodegeneration) biomarkers in the detection of PET Tau positivity status among MA and NHWs

Methods: Data were analyzed from n=401 participants (Total sample [n=21 Tau positive, n=380 Tau negative]; Black [n=11 Tau positive, n=216 Tau negative]; Hispanic [n=5 Tau positive, n=50 Tau negative]; Non-Hispanic whites [n=5 Tau positive, n=114 Tau negative]) from a community-based study of brain aging the Health and Aging Brain Study- Health Disparities (HABS-HD). HABS-HD participants underwent a clinical interview, neuropsychological testing, blood draw, functional medical exam and neuroimaging as a part of the study’s protocol. Plasma blood biomarkers used in this study consisted of Amyloid Beta 40, 42, Total Tau, Ptau181 and NFL derived using Single Molecule Array Technology (SIMOA) on an HDX platform. PET Tau positivity status was determined based on a clinical read. Support Vector Machine (SVM) models were used with plasma ATN biomarkers as predictors of PET Tau positivity status (Positive; Negative). SVM models were run with 10 times, five-fold repeated cross--validation and included models with and without demographics.

Results: In the total sample, ATN biomarkers produced an area under the curve (AUC) of 98% with a sensitivity [SN] of 100% and Specificity [SP] of 73% for distinguishing PET Tau Positive cases from PET Tau Negative. The same ATN biomarkers produced for Black participants an AUC of 98% (SN=100%, SP=80%), for Hispanic participants an AUC of 100% (SN=100%, SP=100%), and for Non-Hispanic White participants an AUC of 98% (SN=100%, SP=70%). The addition of demographic variables of age, gender, and education produced a slight increase in the AUC for both black and non-Hispanic white participants by 1%. The top biomarkers were shown to vary by race and ethnic group.

Conclusions: The results further support the AT(N) biomarkers as a viable method in predicting AD/PET tau positivity, as well as confirming that ptau181 has heavy influence in MA. The varying results of top biomarkers between groups confirm that ethnic background plays a strong role in biomarker profiles contributing to AD. An interesting finding was that demographic factors were ranked higher in black participants in distinguishing PET Tau positivity as compared to NHW and MA. Future work should expand on ptau181 value in relation to MCI state/AD progression in MA.