Amyloid beta (A beta), especially A beta oligomers, is important in early Alzheimer's disease (AD) pathogenesis. AD-associated inflammation has generally been considered as a secondary response to the pathological lesions evoked by A beta oligomers in the early stage of pathogenesis. We studied the levels of plasma A beta monomers, A beta oligomers, and soluble tumor necrosis factor alpha receptors (sTNFRs) in 120 controls, 32 amnestic mild cognitive impairment (aMCI) patients, and 90 mild AD patients. The plasma A beta monomer, oligomer and sTNFR levels were measured by ELISA. We observed that the A beta oligomer levels in mild AD patients were significantly higher than those in aMCI (200.8 +/- 83.8 versus 93.9 +/- 23.3, P<0.05) and healthy subjects (200.8 +/- 83.8 versus 70.0 +/- 60.9, P<0.05). The sTNFR levels in the plasma of aMCI and mild AD patients were significantly higher than the levels of control subjects. Moreover, the levels of both sTNFR1 and sTNFR2 were significantly correlated with A beta oligomer levels in aMCI (sTNFR1 : r=0.376, P=0.034; sTNFR2 : r=0.367, P=0.039) and mild AD patients (sTNFR1 : r=0.471, P<0.001; sTNFR2 : r=0.407, P<0.001). More importantly, changes in A beta oligomer and sTNFR levels accurately differentiated mild AD patients from control subjects, supporting these levels might be potential diagnostic biomarkers for aMCI and AD.