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Interleukin 9 alterations linked to alzheimer disease in african americans.

Artikel i vetenskaplig tidskrift
Författare Whitney Wharton
Alexander L Kollhoff
Umesh Gangishetti
Danielle D Verble
Samsara Upadhya
Henrik Zetterberg
Veena Kumar
Kelly D Watts
Andrea J Kippels
Marla Gearing
J Christina Howell
Monica W Parker
William T Hu
Publicerad i Annals of neurology
Volym 86
Nummer/häfte 3
Sidor 407-418
ISSN 1531-8249
Publiceringsår 2019
Publicerad vid
Sidor 407-418
Språk en
Länkar dx.doi.org/10.1002/ana.25543
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Neurokemi

Sammanfattning

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.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).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.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. ANN NEUROL 2019;86:407-418.

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