Tryptophan degradation and immune activation in Alzheimer's disease

Alzheimer's disease (AD) is likely associated with systemic immune activati on. During immune response, interferon-gamma stimulates indoleamine 2,3-dio xygenase (IDO) converting tryptophan to N-formylkynurenine followed by kynu renine in an ensuing step. Thus, IDO activity is estimated by the kynurenin e per tryptophan quotient (Kyn/Trp). In 21 patients suffering from AD, in 2 0 controls of similar age, and in 49 blood donors we measured serum tryptop han and kynurenine concentrations by HPLC. Lower tryptophan concentrations were found in elderly control subjects compared to blood donors (62.1 vs. 7 3.0 mu M, p < 0.005). Tryptophan concentrations tended to be still lower in AD patients (54.4 mu M, p = 0.07) compared to elderly controls. Enhanced t ryptophan degradation in patients was reflected by significantly increased Kyn/Trp (46.1 vs. 34.1 in elderly controls, p < 0.05). Correlations were fo und in patients between Kyn/Trp and concentrations of soluble immune marker s in serum, i.e., neopterin, interleukin-2 receptor and tumor necrosis fact or receptor tall p < 0.001). Increased Kyn/Trp was associated with reduced cognitive performance. Tryptophan degradation due to immune activation may exert impact on the pathogenesis of AD.