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Authors and affiliations: Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Benjamin EJ, Kiel DP, Wolf PA, Seshadri S. Department of Medicine, Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. [E-mail: ztan@hms.harvard.edu ]

PMID: 17536046

Objective: To examine whether serum cytokines and spontaneous production of peripheral blood mononuclear cell (PBMC) cytokines are associated with the risk of incident Alzheimer disease (AD).

Methods: We followed 691 cognitively intact community-dwelling participants (mean age 79 years, 62% women) and related PBMC cytokine production (tertiles of spontaneous production of interleukin 1 [IL-1], IL-1 receptor antagonist, and tumor necrosis factor [TNF- ]) and serum C-reactive protein and interleukin 6 (IL-6) to the risk of incident AD.

Results: Adjusting for clinical covariates, individuals in the top two tertiles (T2 and T3) of PBMC production of IL-1 or the top tertile (T3) of PBMC production of TNF- were at increased risk of developing AD (multivariable-adjusted hazard ratio [HR] for IL-1 T2 = 2.84, 95% CI 1.09 to 7.43; p = 0.03 and T3 = 2.61, 95% CI 0.96 to 7.07; p = 0.06; for TNF- , adjusted HR for T2 = 1.30, 95% CI 0.53 to 3.17; p = 0.57 and T3 = 2.59, 95% CI 1.09 to 6.12; p = 0.031]) compared with those in the lowest tertile (T1).

Interpretation: Higher spontaneous production of interleukin 1 or tumor necrosis factor by peripheral blood mononuclear cells may be a marker of future risk of Alzheimer disease (AD) in older individuals. These data strengthen the evidence for a pathophysiologic role of inflammation in the development of clinical AD