UBC and AnaSpec Present Poster at ICAD 2008 - August 12, 2008
In a collaborative effort, the University of British Columbia and AnaSpec, Inc. presented a poster at the 2008 International Conference on Alzheimer’s Disease entitled “Alzheimer Disease Tangles and Threads Display Multiple Tau Phosphorylation Sites”. Authored by Jian-Ping Guo, Claudia Schwab, Daniel Hsieh-Hsin Li, Jack Jianyuan Liu, Cecilia Po and Patrick L McGeer, the poster documented the presence of multiple Tau phosphorylation sites in Alzheimer Disease tangles and threads.
As the abstract noted, insoluble tau accumulations are characteristeric of AD and many other tauopathies. They occur primarily in the form of neurofibrillary tangles(NFTs) and threads. Tau is known to be phosphorylated in these abnormal accumulations but it is still uncertain as to which phosphokinases are primarily involved. To explore this question, we epitope mapped a series of anti-tau antibodies directed at specific sites of phosphorylation and compared their ability to detect NFTs and threads in paraformaldehyde fixed sections of AD brain. We synthesized on cellulose membranes an array of 11-mer tau peptides shifted by one amino acid and phosphorylated at key threonine and serine sites. We found that specific antibodies raised against peptides phosporylated at threonine 181, 205, 212, and 217 and at serine 198, 214, and 396 each recognized the specific phosphorylated peptides but not the corresponding non-phosphorylated peptides. By immunohistochemistry, each antibody strongly recognized both NFTs and threads in AD tissue with no apparent qualitative differences. We conclude that each of these threonine and serine sites of tau is abundantly phosphorylated in the threads and NFTs that develop in AD bran. The phosphokinase GSK-3β has been reported to phosphorylate recombinant tau at each of these sites and cdk5 has been reported to phosphorylated all but serine 198, 262 and 400. These phosphokinases could be playing a key role in the development ot tau pathology in AD.
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