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Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.
Seifar, Fatemeh; Fox, Edward J; Shantaraman, Anantharaman; Liu, Yue; Dammer, Eric B; Modeste, Erica; Duong, Duc M; Yin, Luming; Trautwig, Adam N; Guo, Qi; Xu, Kaiming; Ping, Lingyan; Reddy, Joseph S; Allen, Mariet; Quicksall, Zachary; Heath, Laura; Scanlan, Jo; Wang, Erming; Wang, Minghui; Linden, Abby Vander; Poehlman, William; Chen, Xianfeng; Baheti, Saurabh; Ho, Charlotte; Nguyen, Thuy; Yepez, Geovanna; Mitchell, Adriana O; Oatman, Stephanie R; Wang, Xue; Carrasquillo, Minerva M; Runnels, Alexi; Beach, Thomas; Serrano, Geidy E; Dickson, Dennis W; Lee, Edward B; Golde, Todd E; Prokop, Stefan; Barnes, Lisa L; Zhang, Bin; Haroutunian, Varham; Gearing, Marla; Lah, James J; Jager, Philip De; Bennett, David A; Greenwood, Anna; Ertekin-Taner, Nilüfer; Levey, Allan I; Wingo, Aliza; Wingo, Thomas; Seyfried, Nicholas T.
Afiliación
  • 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.
  • Wang M; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Linden AV; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Poehlman W; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Chen X; Sage Bionetworks, Seattle, WA USA.
  • Baheti S; Sage Bionetworks, Seattle, WA 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; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.
  • Beach T; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.
  • Serrano GE; New York Genome Center, New York, NY USA.
  • Dickson DW; Banner Sun Health Research Institute, Sun City, AR USA.
  • Lee EB; Banner Sun Health Research Institute, Sun City, AR USA.
  • Golde TE; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.
  • Prokop S; Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelpha, PA, USA.
  • Barnes LL; Emory University School of Medicine, Atlanta, GA USA.
  • Zhang B; University of Florida, Gainesville, FL USA.
  • Haroutunian V; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.
  • Gearing M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Lah JJ; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Jager P; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  • Bennett DA; Emory University School of Medicine, Atlanta, GA USA.
  • Greenwood A; Emory University School of Medicine, Atlanta, GA USA.
  • Ertekin-Taner N; Columbia University Irving Medical Center, New York, NY USA.
  • Levey AI; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL USA.
  • Wingo A; Sage Bionetworks, Seattle, WA USA.
  • Wingo T; Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL USA.
  • Seyfried NT; Mayo Clinic Florida, Department of Neurology, Jacksonville, FL USA.
bioRxiv ; 2024 Apr 26.
Article en En | MEDLINE | ID: mdl-38712030
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos