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We show here that amyloid beta peptide1-42 (Abeta1-42) may play a key role in the pathogenesis of the cholinergic dysfunction seen in Alzheimer's disease (AD), in addition to its putative role in amyloid plaque formation. Abeta1-42 freshly solubilized in water (non-aged Abeta1-42), which was not neurotoxic without preaggregation, suppressed acetylcholine(More)
Tau protein kinase I (TPKI) isolated from bovine brain has been determined to phosphorylate tau at four distinct sites by detecting modified Ser and Thr residues with protein sequencer. Ser199, Thr231, Ser396 and Ser413 were all found to have been phosphorylated by TPKI (numbering of amino acids was done in relation to the longest human tau [Neuron, 3(More)
According to the amyloid hypothesis for the pathogenesis of Alzheimer disease, beta-amyloid peptide (betaA) directly affects neurons, leading to neurodegeneration and tau phosphorylation. In rat hippocampal culture, betaA exposure activates tau protein kinase I/glycogen synthase kinase 3beta (TPKI/GSK-3beta), which phosphorylates tau protein into Alzheimer(More)
Alzheimer's disease (AD) is characterized by neuronal cell death and two kinds of deposits, neurofibrillary tangles (NFT) and senile plaques. The main component of NFT is paired helical filaments (PHF), which mainly consist of hyperphosphorylated tau protein. Tau protein kinases I and II were found as candidate enzymes responsible for hyperphosphorylation(More)
Using immunohistochemistry, we examined the localization of four types of proline-directed kinases in the brains of control rats and in the brains of non-demented aged human subjects, subjects with Alzheimer's disease and those with Down's syndrome. The four kinases were: cyclin-dependent kinase (cdk) 5, a component of tau protein kinase (TPK) II; TPK(More)
We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho-tau199) by a recently established sandwich ELISA. The(More)
Exposure of rat hippocampal neurons to the peptide amyloid beta (A beta) (25-35) as well as A beta (1-40) peptides enhances phosphorylation of tau to a paired helical filament (PHF)-state through activation of tau protein kinase I (TPK I)/glycogen synthase kinase-3 beta (GSK-3 beta) [Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B.A., Neuron, 14 (1995)(More)
One of the histopathological markers in Alzheimer's disease is the accumulation of hyperphosphorylated tau in neurons called neurofibrillary tangles (NFT) composing paired helical filaments (PHF). Combined tau protein kinase II (TPK II), which consists of CDK5 and its activator (p23), and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate tau to the(More)
One unique phosphorylation site consistently found in paired helical filament tau, serine 413, is modified by tau protein kinase I/glycogen synthase kinase-3 beta but no other known tau kinase. Here we present immunocytochemistry from Alzheimer's disease brains showing that focal subpopulations of hippocampal CA1 pyramidal neurons and neuritic plaques are(More)
Previously, we determined sites of tau protein phosphorylation by tau protein kinase (TPK) I/glycogen synthase kinase 3 beta (GSK-3 beta) and TPKII/(cyclin-dependent kinase 5 (CDK5) + p23). We prepared antibodies specific for these sites of tau phosphorylated by TPKI and TPKII, using chemically synthesized phosphopeptides as antigens. Each antibody(More)