Inflammatory markers and the risk of Alzheimer disease: the Framingham Study.
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).


CONCLUSIONS
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.
Tan
Z S
ZS
Department of Medicine, Institute for Aging Research, Hebrew Senior Life, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02131, USA. ztan@hms.harvard.edu
Beiser
A S
AS
Vasan
R S
RS
Roubenoff
R
R
Dinarello
C A
CA
Harris
T B
TB
Benjamin
E J
EJ
Au
R
R
Kiel
D P
DP
Wolf
P A
PA
Seshadri
S
S
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear; D008297:Male; D009483:Neuropsychological Tests; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein