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Inflammatory markers and the risk of Alzheimer disease

The Framingham Study

From the Department of Medicine, Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center and Harvard Medical School (Z.S.T., D.P.K.), Department of Neurology (S.S., P.A.W., R.A.) and Department of Medicine (R.S.V., E.J.B.), Boston University School of Medicine, Department of Epidemiology and Biostatistics, Boston University School of Public Health (A.B.); Tufts University School of Medicine (R.R.), Boston, MA; National Institute of Aging (T.B.H.), Bethesda, MD; and the University of Colorado Health Sciences Center (C.A.D.), Denver, CO.

Address correspondence and reprint requests to Dr. Zaldy S. Tan, Hebrew Senior Life Department of Medicine, 1200 Centre Street, Boston, MA 02131 ztan{at}hms.harvard.edu

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.

Supported by grants from the National Institute of Neurological Disorders and Stroke (5R01-NS17950), the National Institute of Aging (5R01-AG08122 and 5R01-AG16495), the Boston University Alzheimer's Disease Center (P30 AG13846), and the National Heart, Lung and Blood Institute's Framingham Heart Study (NIH/NHLBI Contract no. N01-HC-25195).

Disclosure: The authors report no conflicts of interest.

Received August 10, 2006. Accepted in final form February 1, 2007.

This article has been cited by other articles:

				E. L. Tobinick, D. L. Menkes, and Z. S. Tan INFLAMMATORY MARKERS AND THE RISK OF ALZHEIMER DISEASE: THE FRAMINGHAM STUDY Neurology, April 1, 2008; 70(14): 1222 - 1223. [Full Text] [PDF]

				P. B. Gorelick and J. V. Bowler Advances in Vascular Cognitive Impairment 2007 Stroke, February 1, 2008; 39(2): 279 - 282. [Full Text] [PDF]

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