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 alpha [TNF-alpha]) 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-alpha 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-alpha, 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 alpha 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.
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 alpha [TNF-alpha]) 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-alpha 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-alpha, 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 alpha 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.
Authors: Daniel C Parker; Michelle M Mielke; Qilu Yu; Paul B Rosenberg; Alka Jain; Constantine G Lyketsos; Neal S Fedarko; Esther S Oh Journal: Int J Geriatr Psychiatry Date: 2012-04-27 Impact factor: 3.485
Authors: Wolfgang Lieb; Alexa S Beiser; Ramachandran S Vasan; Zaldy S Tan; Rhoda Au; Tamara B Harris; Ronenn Roubenoff; Sanford Auerbach; Charles DeCarli; Philip A Wolf; Sudha Seshadri Journal: JAMA Date: 2009-12-16 Impact factor: 56.272
Authors: Gary W Small; Susan Y Bookheimer; Paul M Thompson; Greg M Cole; S-C Huang; Vladimir Kepe; Jorge R Barrio Journal: Lancet Neurol Date: 2008-02 Impact factor: 44.182