Plasma level in demented subjects with Down syndrome Table 3 Comparing mean concentrations, nondemented, prevalent demented and incident demented persons with Down syndrome without epilepsy Citrulline (lM) Arginine (lM) Taurine (lM) Tyrosine (lM) Valine (lM) Methionine (lM) Tryptophan (lM) Phenylanaline (lM) Isoleucine (lM) Leucine (lM) Tryptophan ratio Tyrosine ratio Phe/Tyr Cit/Arg Neopterin (nM) BCAA (lM) AAA (lM) LNAA (lM) Nondemented at baseline n = 276 45.99 (13.4) 73.71 (21.9) 52.88 (12.6) 61.94 (15.7) 234.83 (60.9) 25.25 (5.9) 43.05 (9.5) 60.57 (13.3) 64.49 (18.4) 126.56 (30.2) 8.02 (1.4) 11.88 (2.3) 0.99 (0.1) 0.65 (0.2) 24.74 (10.1) 425.87 (107.2) 165.56 (35.2) 591.43 (136.4) Prevalent demented at baseline n = 38 43.84 (13.9) 78.58 (19.9) 49.82 (11.8) 64.26 (18.1) 228.89 (62.7) 25.66 (7.7) 41.50 (10.6) 61.74 (14.9) 63.05 (15.8) 122.16 (27.8) 7.77 (1.5) 12.64 (3.5) 0.98 (0.2) 0.56 (0.1)a 28.78 (14.4)a 414.10 (103.6) 167.50 (39.4) 581.60 (129.9) 927 Incident demented during follow-up n = 64 48.30 (13.3) 73.70 (19.1) 56.81 (12.8)b,c 64.83 (13.5) 247.20 (56.6) 26.19 (6.4) 43.72 (8.1) 63.09 (11.5) 66.97 (18.2) 129.25 (28.4) 7.82 (1.3) 11.97 (1.9) 0.98 (0.1) 0.66 (0.2)b 25.03 (9.8) 443.42 (100.4) 171.64 (30.0) 615.06 (124.3) Values are mean (standard deviation) Tryptophan ratio tryptophan/ LNAA ratio, tyrosine ratio tyrosine/LNAA ratio, Phe/Tyr phenylanaline/tyrosine ratio, Cit/Arg citrulline/arginine ratio, BCAA summed concentration of leucine, isoleucine and valine lM/l, AAA summed concentration of phenylanaline, tyrosine, tryptophan lM/l, LNAA large neutral amino acids: summed concentration of phenylalanine, tyrosine, tryptophan, valine, leucine and isoleucine lM/l a Mann–Whitney U-test, P \ 0.05 prevalent demented compared with the group of nondemented persons with Down syndrome b Mann–Whitney U-test, P \ 0.05 incident demented compared with the group of prevalent demented persons with Down syndrome c Mann Whitney U-test, P \ 0.05 incident demented compared with the group of nondemented persons with Down syndrome phenylalanine to tyrosine. This is in line with the increased phenylalanine levels in the demented as compared to the healthy DS subjects. Possible mechanisms for the impaired bioavailability of BH4 are oxidation of the labile substance BH4 due to the oxidative stress and/or depletion of BH4 due to the higher neopterin synthesis at the expense of BH4 (Ploder et al. 2008; Shi et al. 2004). Since the Cit/Arg ratio is signiﬁcantly higher in the incident demented cases and assuming that this ratio is a good reﬂection of NO synthesis indeed, it can be hypothesized that the production of NO is enhanced during the early development of dementia. The plasma concentration of taurine is increased espe- cially in the subgroup of incident dementia (Table 3). The ﬁnding of an increased level of taurine may be syndrome speciﬁc since similar observations have been reported previously (Coppus et al. 2007; Mircher et al. 1997). It has been suggested that taurine may prevent neurotoxicity of beta-amyloid (Louzada et al. 2004) and may decrease beta- amyloid aggregation (Santa-Maria et al. 2007). The BCAA concentration is not different in the various subgroups but decreases with age. Since several decades it has been suggested from animal studies that a lower plasma level of BCAA may result in immune impairment (Jose and Good 1973; Li et al. 2007).Whether the observation of diminished BCAA in the group of older DS subjects reﬂects a syndrome speciﬁc impaired immune function is not clear. This may also be the consequence of dietary factors albeit that both in the present study as in the pre- vious one, a large difference between healthy controls and DS subjects was found in the BCAA levels. In conclusion, the results of the present study demon- strate again that plasma levels of nearly all measured amino acids in DS subjects differ substantially from those in healthy controls. Moreover, in demented DS individuals an additional increase of taurine is observed, while during development of clinical dementia changes in levels of biochemical parameters related to NO metabolism and oxidative stress occur. 123