학술논문
Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.
Document Type
Author
Seifar F; Emory University School of Medicine, Atlanta, GA USA.; Fox EJ; Emory University School of Medicine, Atlanta, GA USA.; Shantaraman A; Emory University School of Medicine, Atlanta, GA USA.; Liu Y; Emory University School of Medicine, Atlanta, GA USA.; Dammer EB; Emory University School of Medicine, Atlanta, GA USA.; Modeste E; Emory University School of Medicine, Atlanta, GA USA.; Duong DM; Emory University School of Medicine, Atlanta, GA USA.; Yin L; Emory University School of Medicine, Atlanta, GA USA.; Trautwig AN; Emory University School of Medicine, Atlanta, GA USA.; Guo Q; Emory University School of Medicine, Atlanta, GA USA.; Xu K; Emory University School of Medicine, Atlanta, GA USA.; Ping L; Emory University School of Medicine, Atlanta, GA USA.; Reddy JS; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Allen M; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Quicksall Z; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Heath L; Sage Bionetworks, Seattle, WA USA.; Scanlan J; Sage Bionetworks, Seattle, WA USA.; Wang E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Wang M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Linden AV; Sage Bionetworks, Seattle, WA USA.; Poehlman W; Sage Bionetworks, Seattle, WA USA.; Chen X; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Baheti S; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Ho C; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Nguyen T; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Yepez G; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Mitchell AO; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Oatman SR; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Wang X; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Carrasquillo MM; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Runnels A; New York Genome Center, New York, NY USA.; Beach T; Banner Sun Health Research Institute, Sun City, AR USA.; Serrano GE; Banner Sun Health Research Institute, Sun City, AR USA.; Dickson DW; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Lee EB; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelpha, PA, USA.; Golde TE; Emory University School of Medicine, Atlanta, GA USA.; Prokop S; University of Florida, Gainesville, FL USA.; Barnes LL; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.; Zhang B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Haroutunian V; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.; Gearing M; Emory University School of Medicine, Atlanta, GA USA.; Lah JJ; Emory University School of Medicine, Atlanta, GA USA.; Jager P; Columbia University Irving Medical Center, New York, NY USA.; Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.; Greenwood A; Sage Bionetworks, Seattle, WA USA.; Ertekin-Taner N; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.; Mayo Clinic Florida, Department of Neurology, Jacksonville, FL USA.; Levey AI; Emory University School of Medicine, Atlanta, GA USA.; Wingo A; Emory University School of Medicine, Atlanta, GA USA.; Wingo T; Emory University School of Medicine, Atlanta, GA USA.; Seyfried NT; Emory University School of Medicine, Atlanta, GA USA.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial and ethnic groups.
Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS).
Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals.
Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.
Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS).
Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals.
Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.