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Author Notes:

William Hu, MD, PhD, Department of Neurology, 615 Michael Street, 505F, Atlanta, GA 30322, Phone 404-727-4174, Fax 404-727-3728, william.hu@emory.edu

WW, SU, KDW, MG, MWP, and WTH contributed to study concept and design; WW, ALK, UG, DDV, SU, HZ, VK, KDW, AJK, MG, JCH, MWP, and WTH contributed to data acquisition and analysis; WW, ALK, UG, DDV, SU, VK, JCH, MWP, and WTH contributed to drafting the manuscript and figures.

The authors wish to acknowledge Allan I. Levey, MD, PhD; James J. Lah, MD, PhD; Chadwick Hales, MD, PhD; Jonathan D. Glass, MD; and James Newman, BS for collecting data and general support.

Dr. Hu consults for ViveBio, LLC. which manufactures lumbar puncture trays.

Subject:

Research Funding:

This work was supported by National Institutes of Health [AG43885, AG42856, AG25688, K01AG042498].

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology
  • GENOME-WIDE ASSOCIATION
  • IDENTIFIES VARIANTS
  • FLUID BIOMARKER
  • TGF-BETA
  • T-CELLS
  • IL-9
  • EXPRESSION
  • CLU

Interleukin 9 alterations linked to alzheimer disease in african americans

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Journal Title:

Annals of Neurology

Volume:

Volume 86, Number 3

Publisher:

, Pages 407-418

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Objective: Compared to older Caucasians, older African Americans have higher risks of developing Alzheimer disease (AD) and lower cerebrospinal fluid (CSF) tau biomarker levels. It is not known whether tau-related differences begin earlier in life or whether race modifies other AD-related biomarkers such as inflammatory proteins. Methods: We performed multiplex cytokine analysis in a healthy middle-aged cohort with family history of AD (n = 68) and an older cohort (n = 125) with normal cognition (NC), mild cognitive impairment, or AD dementia. After determining baseline interleukin (IL)-9 level and AD-associated IL-9 change to differ according to race, we performed immunohistochemical analysis for proteins mechanistically linked to IL-9 in brains of African Americans and Caucasians (n = 38), and analyzed postmortem IL-9–related gene expression profiles in the publicly available Mount Sinai cohort (26 African Americans and 180 Caucasians). Results: Compared to Caucasians with NC, African Americans with NC had lower CSF tau, p-Tau181, and IL-9 levels in both living cohorts. Conversely, AD was only correlated with increased CSF IL-9 levels in African Americans but not Caucasians. Immunohistochemical analysis revealed perivascular, neuronal, and glial cells immunoreactive to IL-9, and quantitative analysis in independent US cohorts showed AD to correlate with molecular changes (upstream differentiation marker and downstream effector cell marker) of IL-9 upregulation only in African Americans but not Caucasians. Interpretation: Baseline and AD-associated IL-9 differences between African Americans and Caucasians point to distinct molecular phenotypes for AD according to ancestry. Genetic and nongenetic factors need to be considered in future AD research involving unique populations.

Copyright information:

© 2019 American Neurological Association

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