In Alzheimer disease (AD) brain, activities of protein phosphatase (PP)-2A/PP-1 which are known to be associated with microtubules are compromised and are probably a cause of neurofibrillary degeneration through hyperphosphorylation of microtubule proteins. In the present study, an increase of ∼11 pmol phosphate/μg protein in 100 000×g pellet from AD compared with age-matched control brains was found. Tau protein, which is hyperphosphorylated in AD can only account for ∼4 pmol phosphate/μg protein, suggesting the presence of non-tau hyperphosphorylated proteins in the diseased brain. Western blot analysis with phosphoserine antibodies revealed a ∼54 kDa non-tau protein to be significantly hyperphosphorylated in AD compared with age-matched control cases in the particulate fraction. The ∼54 kDa protein was purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified as β-tubulin by immunolabeling with specific antibodies, mass spectrometry analysis and by N-terminal amino acid sequencing. The purified protein was hyperphosphorylated at serine residues in AD. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Vijayan, S., El-Akkad, E., Grundke-Iqbal, I., & Iqbal, K. (2001). A pool of β-tubulin is hyperphosphorylated at serine residues in Alzheimer disease brain. FEBS Letters, 509(3), 375–381. https://doi.org/10.1016/S0014-5793(01)03201-X