Proteomic Profiles of Neurodegeneration Among Mexican Americans and Non-Hispanic Whites in the HABS-HD Study

Abstract

Background: Hispanics are expected to experience the largest increase in Alzheimer's disease (AD) and AD related dementias over the next several decades. However, few studies have examined biomarkers of AD among Mexican Americans, the largest segment of the U.S. Hispanic population.

Objective: We sought to examine proteomic profiles of an MRI-based marker of neurodegeneration from the AT(N) framework among a multi-ethnic, community-dwelling cohort.

Methods: Community-dwelling Mexican Americans and non-Hispanic white adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T MRI of the brain. A neurodegeneration MRI meta-ROI biomarker for the AT(N) framework was calculated.

Results: Data was examined from n = 1,291 participants. Proteomic profiles were highly accurate for detecting neurodegeneration (i.e., N+) among both Mexican Americans (AUC = 1.0) and non-Hispanic whites (AUC = 0.98). The proteomic profile of N + was different between ethnic groups. Further analyses revealed that the proteomic profiles of N + varied by diagnostic status (control, MCI, dementia) and ethnicity (Mexican American versus non-Hispanic whites) though diagnostic accuracy was high for all classifications.

Conclusion: A proteomic profile of neurodegeneration has tremendous value and point towards novel diagnostic and intervention opportunities. The current findings demonstrate that the underlying biological factors associated with neurodegeneration are different between Mexican Americans versus non-Hispanic whites as well as at different levels of disease progression.

Keywords: Alzheimer’s disease; biomarkers; diversity; hispanic; mexican american; mild cognitive impairment; neurodegeneration.

Figure 1.

Proteomic profiles were derived from SVM analyses in the total sample. The SVM variable importance plot and AUC were included in Figure 1 along with the confusion matrix and class statistics of sensitivity, specificity and negative predictive value for the blood-based profile of neurodegeneration for the entire cohort.

Figure 2.

Proteomic profiles were derived from SVM analyses split by ethnic groups. The SVM variable importance plot and AUC were included for blood-based profiles of neurodegeneration in Figure 2a for Non-Hispanic Whites and Figure 2b for Mexican Americans along with the confusion matrix and class statistics of sensitivity, specificity and negative predictive value.

Figure 3.

Proteomic profiles derived from SVM analyses are presented for neurodegeneration separated by cognitive diagnosis of normal cognition (Figure 3a), mild cognitive impairment (Figure 3b), and dementia (Figure 3c). The SVM variable importance plot and AUC were included for the blood-based profiles of neurodegeneration for each diagnostic group along with the confusion matrix and class statistics of sensitivity, specificity and negative predictive value.

Figure 4.

Proteomic profiles derived from SVM analyses split by both ethnicity group and diagnostic status. The SVM variable importance plot and AUC were reported for each ethnic group and cognitive diagnosis (non-Hispanic white [NHW], normal control Figure 4a; NHW, Mild Cognitive Impairment [MCI] Figure 4b; NHW, Dementia Figure 4c; Mexican American [MA], normal control Figure 4d; MA, MCI Figure 4e; MA, Dementia Figure 4d).