In vivo oxidative modification of brain in transgenic and non-transgenic mice: role of Met-35 of Aβ. Oxidative stress is indexed by: (a) Protein Carbonylation. Results show a significant increase in the levels of protein carbonyls in Tg PDAPP(J20) mice (n=10) compared to age-matched Non Tg PDAPP controls (n=5; *P<0.003). Tg PDAPP(M631L) mice (n=10) did not show a significant increase in protein carbonyls compared to their respective Non Tg PDAPP(M631L) controls (n=5; P<0.35), but did, however, have significantly reduced protein carbonyl levels compared to age-matched Tg PDAPP(J20) mice (**P<0.0004). Non-transgenic control values were set to 100 percent, to which transgenic values were compared. These data are presented as mean ± S.E.M. Statistical analyses employed Student’s two-tailed t-test. (b) Lipid peroxidation as indexed by protein-bound HNE. A significant increase in the levels of protein-bound HNE in Tg PDAPP(J20) mice (n=10) compared to age-matched Non Tg PDAPP(J20) controls (n=5; *P<0.02) was found; however, Tg PDAPP(M631L) mice (n=10) did not show a significant change in protein-bound HNE levels compared to Non Tg PDAPP(M631L) controls (n=5; P<0.95). Moreover, there were significantly reduced protein-bound HNE levels in Tg PDAPP(M631L) mice compared to age-matched Tg PDAPP(J20) mice (**P<0.04). Non-transgenic control values were set to 100 percent, to which transgenic values were compared. These data are presented as mean ± S.E.M. Statistical analyses employed Student’s two-tailed t-test. (c) Protein-resident 3-NT in brain. In agreement with both protein carbonyl and protein-bound HNE parameters, a significant increase in Tg PDAPP(J20) mouse (n=10) 3-NT levels was found compared to age-matched Non Tg PDAPP(J20) controls (n=5; *P<0.002). In contrast, Tg PDAPP(M631L) mice (n=10) did not show a significant change in 3-NT levels compared to Non Tg PDAPP(M631L) controls (n=5; P<0.76), while a significant reduction in Tg PDAPP(M631L) 3-NT levels compared to age-matched Tg PDAPP(J20) mice was observed (**P<0.0001). Non-transgenic control values were set to 100 percent, to which transgenic values were compared. These data are presented as mean ± S.E.M. Statistical analyses employed Student’s two-tailed t-test.