TDP-43 Pathology in the Setting of Intermediate and High Alzheimer’s Disease Neuropathologic Changes: A Preliminary Evaluation Across Ethnoracial Groups

Article type: Research Article

Authors: Huie, Emily Z.^a | Escudero, Anthony^{a; c} | Saito, Naomi^b | Harvey, Danielle^{b; c} | Nguyen, My-Le^a | Lucot, Katherine L.^a | LaGrande, Jayne^c | Mungas, Dan^c | DeCarli, Charles^c | Lamar, Melissa^{d; e} | Schneider, Julie A.^{e; f; g} | Kapasi, Alifiya^{e; f} | Rissman, Robert A.^h | Teich, Andrew F.ⁱ | Dugger, Brittany N.^{a; c; *}

Affiliations: [a] Department of Pathology and Laboratory Medicine, University of California Davis, School of Medicine, Sacramento, CA, USA | [b] Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, CA, USA | [c] Alzheimer’s Disease Research Center, Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA | [d] Department of Psychiatry and Behavioral Sciences, Rush Medical College, Chicago, IL, USA | [e] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [f] Department of Pathology, Rush University Medical Center, Chicago, IL, USA | [g] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA | [h] Department of Neurosciences, University of California San Diego, San Diego, La Jolla, CA, USA | [i] Taub Institute for Research on Alzheimer’s Disease and Aging Brain, Department of Neurology, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA

Correspondence: [*] Correspondence to: Brittany N. Dugger, PhD, Department of Pathology and Laboratory Medicine University of California, Davis, 4645 2nd Ave., 3400A Research Building III, Sacramento, CA 95817, USA. Tel.: +1 916 734 3855; E-mail: [email protected].

Abstract: Background:Transactive Response DNA Binding Protein 43 kDa (TDP-43) pathology is frequently found in cases with Alzheimer’s disease (AD). TDP-43 pathology is associated with hippocampal atrophy and greater AD severity denoted by cognition and clinical representation. Current TDP-43 pathology studies are predominantly based on non-Hispanic White cohorts. Objective:We sought to evaluate the presence of TDP-43 pathology across ethnoracial groups utilizing the National Alzheimer’s Coordinating Center; a database containing data from over 29 institutions across the United States. Cases (N = 1135: Hispanics/Latinos = 29, African Americans/Black Americans = 51, Asians/Asian Americans = 10, American Indians/Alaskan Natives = 2, non-Hispanic White = 1043) with intermediate/high AD having data on TDP-43 pathology in the amygdala, hippocampus, entorhinal cortex, and neocortex were included. Methods:TDP-43 pathology frequency in each neuroanatomic region among ethnoracial groups were compared using generalized linear mixed effects models with center as a random effect adjusting for age at death, education, and gender. Results:Although groups were imbalanced, there was no significant difference across ethnoracial groups based on TDP-43 pathology (p = 0.84). With respect to neuroanatomical regions evaluated, there were no significant differences across ethnoracial groups (p-values > 0.06). There were also no significant differences for age at death and gender ratios across ethnoracial groups based on TDP-43 pathology. Although not statistically significant, TDP-43 pathology was present less often in Hispanic/Latinos (34%) when compared to non-Hispanic Whites (46%). Conclusion:While this is a preliminary evaluation, it highlights the need for diverse cohorts and on TDP-43 pathology research across ethnoracial groups. This is the first study to our knowledge having a focus on the neuroanatomical distribution of TDP-43 deposits in Hispanic/Latino decedents with AD.

Keywords: African American, Alzheimer’s disease, Asian, brain, cohort studies, Hispanic, Latino, minoritized groups, neuropathology

DOI: 10.3233/JAD-220558

Journal: Journal of Alzheimer's Disease, vol. 91, no. 4, pp. 1291-1301, 2023