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

Article type: Research Article

Authors: O’Bryant, Sid E.^{a; *} | Zhang, Fan^{a; b} | Petersen, Melissa^{a; b} | Hall, James R.^{a; c} | Johnson, Leigh A.^{a; c} | Yaffe, Kristine^{d; e} | Braskie, Meredith^f | Vig, Rocky^g | Toga, Arthur W.^h | Rissman, Robert A.^{i; j} | for the HABS-HD Study Team¹

Affiliations: [a] Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, USA | [b] Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA | [c] Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA | [d] Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA | [e] San Francisco VA Medical Center, San Francisco, CA, USA | [f] Imaging Genetics Center, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA | [g] Imaging, Midtown Medical Imaging, Fort Worth, TX, USA | [h] Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA | [i] Department of Neurosciences, University of California, San Diego, La Jolla, CA and Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [j] Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

Correspondence: [*] Correspondence to: Sid O’Bryant, PhD, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107 USA. Tel.: +1 817 735 2962; E-mail: [email protected].

Note: [1] HABS-HD Study Team: MPIs: Sid E O’Bryant, Kristine Yaffe, Arthur Toga, Robert Rissman, & Leigh Johnson; and the HABS-HD Investigators: Meredith Braskie, Kevin King, James R Hall, Matthew Borzage, Melissa Petersen, Raymond Palmer, Robert Barber, Raul Vintimilla, Yonggang Shi, Fan Zhang, Rajesh Nandy, Roderick McColl, David Mason, Bradley Christian, Nicole Philips and Stephanie Large.

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

DOI: 10.3233/JAD-210543

Journal: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 1243-1254, 2022