Interleukin 9 alterations linked to alzheimer disease in african americans
| Autor: | William T. Hu, Veena Kumar, Danielle D. Verble, Alexander L. Kollhoff, Henrik Zetterberg, Monica W. Parker, Samsara Upadhya, Andrea J. Kippels, Marla Gearing, Kelly D. Watts, Umesh Gangishetti, J. Christina Howell, Whitney Wharton |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment tau Proteins White People Article 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Humans Dementia Cognitive Dysfunction Interleukin 9 Family history Aged business.industry Interleukin-9 Brain Interleukin Middle Aged medicine.disease Black or African American 030104 developmental biology Cytokine Neurology Immunology Cohort Biomarker (medicine) Female Neurology (clinical) Alzheimer's disease business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Annals of Neurology. 86:407-418 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/ana.25543 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text