Affiliations: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA
Correspondence:
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Corresponding author: Dr. Gail V.W. Johnson, Department Psychiatry, SC 1061, 1720 7th Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA, Tel.: +1 205 934 2465, Fax: +1 205 934 3709, E-mail: gvwj@uab.edu.
Note: [*] This article is published with permission from the University of Kentucky. It is also published in the online journal Alzheimer's Disease Review; www.coa.uky.edu/ADReview/.
Abstract: In 1975, Weingarten and colleagues isolated a protein factor that was able to induce microtubule formation. They called this factor tau (t). Some ten years later a new era of research on this microtubule-associated protein was launched when several groups almost simultaneously discovered that tau was the predominant protein component of the paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) which are characteristic pathological lesions of the Alzheimer's disease brain. Subsequent findings that PHF-tau isolated from Alzheimer's disease brain was phosphorylated to a greater extent than non-PHF tau, led to extensive investigation into the posttranslational modifications (mainly phosphorylation) of tau in normal and Alzheimer's disease brain. The present review highlights the literature concerning the normal functioning and processing of tau protein, and examines the evidence for the involvement of the abnormal posttranslational processing of tau in the pathology of Alzheimer's disease. Finally, speculation as to the relationship between abnormal processing of tau, other subcellular abnormalities seen in Alzheimer's disease, and the pathological causes of the disease are discussed.
