SUBCELLULAR-DISTRIBUTION OF PROTEIN PHOSPHATASES AND ABNORMALLY PHOSPHORYLATED-TAU IN THE TEMPORAL CORTEX FROM ALZHEIMERS-DISEASE AND CONTROL BRAINS

Microtubule-associated protein tau is abnormally hyperphosphorylated i n the brain of patients with Alzheimer's disease (AD). In vitro studie s have shown that protein phosphatases PP-2A and PP-2B can convert Alz heimer like tau to its normal state and that the activities of PP-1, P P-2A, and phosphotyrosyl-protein phosphatase (PTP) are reduced in AD b rain. However, to have a direct effect on the regulation of phosphoryl ation on tau, these enzymes have to exist in neurons. Using specific p olyclonal antibodies the levels of protein phosphatases PP-1, PP-2A, a nd PP-2B were determined by indirect ELISA in superior temporal cortic al gray matter of AD and control brains. The protein levels of PP-2A a nd PP-2B were significantly increased in postsynaptosomal supernatant 2 (S2) of the AD group, and this alteration showed a significant linea r correlation with levels of hyperphosphorylated tau. PP-1 and PTP-1B levels were not significantly changed in any of the AD fractions. Beca use of the large variation from case to case, the activity levels of n one of the phosphatases investigated were significantly different betw een the AD and control groups. However, the PP-2B specific activity (a ctivity/protein) showed a significant linear inverse correlation with hyperphosphorylated tau. These studies suggest that any attempt by the AD brain to compensate for the decreased tau phosphatase activity rem ains unsuccessful and that the decrease in phosphatase activity might contribute to increased levels of abnormally phosphorylated tau.