Hyun-Sik Yang1,2,3, Can Zhang3,4, Becky C Carlyle3,5, Sherri Y Zhen4, Bianca A Trombetta5, Aaron P Schultz1,3,6, Jeremy J Pruzin1,2,3, Colleen D Fitzpatrick1,2, Wai-Ying W Yau1,2,3, Dylan R Kirn1,2, Dorene M Rentz1,2,3, Steven E Arnold3,5, Keith A Johnson1,2,3,6, Reisa A Sperling1,2,3,6, Jasmeer P Chhatwal1,2,3, Rudolph E Tanzi3,4. 1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. 2. Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA. 3. Harvard Medical School, Boston, Massachusetts, USA. 4. Genetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA. 5. Alzheimer's Clinical and Translational Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA. 6. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Abstract
INTRODUCTION: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aβ), remains unclear. METHODS: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aβ. We next examined associations between cytokine levels and neuroimaging biomarkers of Aβ/tau/neurodegeneration. RESULTS: Higher IL-12p70 was associated with slower cognitive decline in the setting of higher Aβ (false discovery rate [FDR] = 0.0023), whereas higher IFN-γ was associated with slower cognitive decline independent of Aβ (FDR = 0.013). Higher IL-12p70 was associated with less tau and neurodegeneration in participants with higher Aβ. DISCUSSION: Immune dysregulation is implicated in early-stage cognitive decline, and greater IL-12/IFN-γ axis activation may be protective against cognitive decline and early-stage AD progression.
INTRODUCTION: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aβ), remains unclear. METHODS: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aβ. We next examined associations between cytokine levels and neuroimaging biomarkers of Aβ/tau/neurodegeneration. RESULTS: Higher IL-12p70 was associated with slower cognitive decline in the setting of higher Aβ (false discovery rate [FDR] = 0.0023), whereas higher IFN-γ was associated with slower cognitive decline independent of Aβ (FDR = 0.013). Higher IL-12p70 was associated with less tau and neurodegeneration in participants with higher Aβ. DISCUSSION: Immune dysregulation is implicated in early-stage cognitive decline, and greater IL-12/IFN-γ axis activation may be protective against cognitive decline and early-stage AD progression.
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