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. ANN NEUROL 2019;86:407-418.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Wharton W,Kollhoff AL,Gangishetti U,Verble DD,Upadhya S,Zetterberg H,Kumar V,Watts KD,Kippels AJ,Gearing M,Howell JC,Parker MW,Hu WTdoi
10.1002/ana.25543subject
Has Abstractpub_date
2019-09-01 00:00:00pages
407-418issue
3eissn
0364-5134issn
1531-8249journal_volume
86pub_type
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journal_title:Annals of neurology
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更新日期:1984-06-01 00:00:00
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