Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease.
In this study, we have evaluated the levels of blood histamine, serum interleukin-1 beta (IL-1 beta), and plasma tumor necrosis factor-alpha (TNF-alpha) in 20 patients with mild to moderate Alzheimer disease (AD; 13 early onset and 7 late-onset AD subjects) and in 20 age-matched control subjects (C). AD patients showed higher concentrations of histamine (AD = 452.9 +/- 237.9 pmol/mL; C = 275.3 +/- 151.5 pmol/mL; p < 0.05) and IL-1 beta (AD = 211.2 +/- 31.1 pg/mL; C = 183.4 +/- 24.4 pg/mL; p < 0.01), and lower values of TNF-alpha (AD = 3.59 +/- 2.02 pg/mL; C = 9.47 +/- 2.64 pg/mL; p < 0.001) than elderly controls. Increased levels of histamine and decreased levels of TNF-alpha were observed in both early onset AD (EOAD) and late-onset AD (LOAD) patients, but only EOAD subjects had elevated serum IL-1 beta values compared with age-matched controls. Age negatively correlated with histamine (r = -0.57; p < 0.05) and positively with IL-1 beta levels (r = 0.48; p < 0.05) in healthy subjects, but not in AD, whereas a positive correlation between TNF-alpha scores and age was only found in AD patients (r = 0.46; p < 0.05). Furthermore, histamine and TNF-alpha values correlated negatively in AD (r = -0.50, p < 0.05). In addition, cognitive impairment increased in patients with lower TNF-alpha and higher histamine and IL-1 beta levels, as indicated by the correlations between mental performance scores and histamine (r = -0.37, ns), IL-1 beta (r = -0.33, ns) and TNF-alpha levels (r = 0.42, p < 0.05). Finally, histamine concentrations decreased as depression scores increased in AD (r = -0.63, p < 0.01). These data suggest a dysfunction in cytokine and histamine regulation in AD, probably indicating changes associated with inflammatory processes.
Alvarez
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EuroEspes Research Center, Santa Marta de Babío, A Coruña, Spain. euroespes@lcg.servicom.es
Franco
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Fernández-Novoa
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Cacabelos
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D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000503:physiopathology / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D003071:Cognition; D005260:Female; D006632:Histamine / Q000097:blood*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015415:Biomarkers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine