Alzheimer's Disease Neurofibrillary Tangles Contain Mitosis-Specific Phosphoepitopes
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 67, Issue 6, pages 2405–2416, December 1996
How to Cite
Kondratick, C. M. and Vandré, D. D. (1996), Alzheimer's Disease Neurofibrillary Tangles Contain Mitosis-Specific Phosphoepitopes. Journal of Neurochemistry, 67: 2405–2416. doi: 10.1046/j.1471-4159.1996.67062405.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received May 6, 1996; final revised manuscript received July 16, 1996; accepted July 17, 1996.
- Alzheimer's disease;
- Neurofibrillary tangles;
- Microtubule-associated protein τ;
- Paired helical filaments;
Abstract: Paired helical filaments (PHFs) are the major components of neurofibrillary lesions present in Alzheimer's disease (AD). PHFs are composed of the microtubule-associated protein (MAP) τ, which is abnormally phosphorylated in AD. Normal fetal τ is also phosphorylated and shares certain phosphoepitopes with PHF-τ. The abnormal phosphorylation of PHF-τ is considered to be involved in the formation of PHFs and subsequent degeneration of AD neurons. We have previously shown that other neuronal MAPs, such as MAP1B, contain mitosis-specific phosphoepitopes. In addition to mitotic cells, these epitopes are also expressed in fetal brain and PC12 cells during differentiation and neurite outgrowth. One hypothesis regarding the etiology of AD involves the reactivation of a fetal-like state and mitotic conditions in selected neurons. To determine if similar mitosis-associated phosphoepitopes appeared in AD, sections of hippocampal tissue were stained for immunoreactivity with antibodies recognizing both τ and mitotic phosphoepitopes. Both the MPM2 mitotic phosphoepitope antibody and the AT8 PHF-τ antibody stained neurofibrillary lesions and colocalized to pyramidal neurons in AD samples. In addition, PHFs isolated from an AD brain reacted with both antibodies. The MPM2 antibody specifically reacted with τ in the isolated PHF fraction but not normal adult τ. In addition, MPM2 failed to react with normal fetal or adult τ obtained from rat brains. The MPM2 antibody also recognized human MAP1B; however, MAP1B was not present in the PHF fraction. Our results indicate that MPM2 recognized a phosphoepitope present on PHF-τ. Because normal fetal or adult rat brain τ did not express the MPM2 epitope, it is likely that this phosphoepitope is specific for the disease state.