Utility of Blood Based Biomarkers in Detecting Cerebral Amyloid among Mexican Americans: A HABS-HD Study

Background: Alzheimer's disease (AD) is the leading cause of dementia in our nation's aging population. Minority groups, such as Hispanics, are 1.5 times more likely than non-Hispanic whites (NHW) to develop AD during their lifetime. Several studies have shown that blood biomarkers can be used to detect dementia related to AD. However, limited research has analyzed the relationship between blood biomarkers and cerebral amyloid, an AD biomarker, in minority groups. This study aims to address this gap and examine the utility of blood-based biomarkers to detect cerebral amyloid and predict AD among NHW and Mexican Americans (MA). Methods: Data were analyzed on 232 participants (n=148 NHW; n=84 MA) from the Health & Aging Brain Study – Health Disparities (HABS-HD) study. Of those selected for inclusion in this study, 46 participants had a positive cerebral amyloid scan, while 186 had a negative scan. Plasma samples were assayed for amyloid beta (Aβ)40, Aβ42, total tau (t-tau), phosphorylated tau (p-tau181), and neurofilament light (NfL) using the Simoa (single molecule array) technology platform (Quanterix.com). PET amyloid imaging was performed using a Neuraceq (florbetaben) tracer to measure cerebral amyloid positivity based on a clinical read and global standardized uptake value ratios (SUVRs). Covariates included age, gender, and education. Certain models were also split by ethnic groups. Correlation models were run separately for each blood biomarker and total cerebral amyloid SUVR. The plasma proteomic profiles were generated without transformations using Random forest (RF) analysis in R package. Regression coefficients examined the relationship between the proteomic biomarkers, the independent variable, and cerebral amyloid, the dependent variable. Logistic regressions were conducted to examine the ability of the proteomic profiles to predict cerebral amyloid positivity status. Results: Biomarkers Aβ40, Aβ42, p-tau181, and NfL were all significantly correlated with cerebral amyloid (ps< 0.05). The entire cohort had a high regression performance (R2=0.905) between the proteomic biomarkers and cerebral amyloid, with p-tau181 as the driving biomarker. Among the MA group, the biomarkers comprising the proteomic profile yielded excellent accuracy in detecting cerebral amyloid (Area Under the Curve [AUC] = 1.00, Sensitivity [SN] = 1.00, Specificity [SP] = 0.97, and positive predictive value [PPV] = 88%). Among the NHW group, the biomarkers also detected cerebral amyloid with a high level of accuracy (AUC = 0.99, SN = 1, SP = 0.99, and PPV = 92%). Cerebral amyloid positivity was predicted with 100% accuracy in both groups, with false positive rates of 1.19% and 2.03% in the MA and NHW groups, respectively. Conclusions: This study supports the application of plasma proteomic profiles to predict cerebral amyloid-related to AD. The findings highlighted that p-tau181 is the most important biomarker for cerebral amyloid detection in the MA population. This is relevant as prior work in NHW have focused on Aβ being the primary biomarker for AD detection. Future work should examine these findings in a larger population subset in order to validate the predictive utility of blood biomarkers as a screening tool in clinical settings for early AD detection.