Levels of tau phosphorylation at different sites in Alzheimer disease brain

THE microtubule-associated protein tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) brain. To date, 21 phosphorylated sites of tau have been identified. In the present study the levels of phosphorylation at Ser(199)/Ser(202), Thr(231)/Ser(235), Ser(262)/Ser(356) and Ser(196)/Ser(404) of tau in AD brain homogenate and its 100 000 x g supernatant were determined using radioimmuno-dot-blot assay. In homogenate, Ser(199)/Ser(202) and Ser(262)/Ser(356) were phosphorylated to similar level and were more phosphorylated than Thr(231) Or Ser(396)/Ser(404). In supernatant, there was no significant difference in phosphorylated tau level among the investigated sites except for Thr(231)/Ser(235) which was least phosphorylated. These results suggest that Ser(199)/Ser(202) and Ser(262)/Ser(356) are major sites of phosphorylation of tan in AD brain. NeuroReport 9: 2375-2379 (C) 1998 Rapid Science Ltd.