Aging
Navigate
Submit an Article
Research Paper|Volume 1, Issue 4|pp 382—388

Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease

David J. Bonda1, Teresa A. Evans1, Corrado Santocanale2, Jesús Catalá Llosá3, Jose Viňa3, Vladan P. Bajic4, Rudy J. Castellani5, Sandra L. Siedlak1, George Perry1,6, Mark A. Smith1, Hyoung-gon Lee1
  • 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
  • 2National Centre for Biomedical Engineering and Science, National University of Ireland Galway, Galway, Ireland
  • 3Departamento de Fisiología, Facultad de Medicina, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain
  • 4Institute of Biomedical Research, Galenika a.d., 11000 Belgrade, Serbia
  • 5Department of Pathology, University of Maryland, Baltimore, MD 21250, USA
  • 6College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249, USA
Received: April 2, 2009Accepted: April 23, 2009Published: April 23, 2009
https://doi.org/10.18632/aging.100044

Copyright: © 2009 Bonda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aberrant neuronal re-entry into the cell cycle is emerging as a potential pathological mechanism in Alzheimer disease (AD). However, while cyclins, cyclin dependent kinases (CDKs), and other mitotic factors are ectopically expressed in neurons, many of these proteins are also involved in other pathological and physiological processes, generating continued debate on whether such markers are truly indicative of a bona fide cell cycle process. To address this issue, here we analyzed one of the minichromosome maintenance (Mcm) proteins that plays a role in DNA replication and becomes phosphorylated by the S-phase promoting CDKs and Cdc7 during DNA synthesis. We found phosphorylated Mcm2 (pMcm2) markedly associated with neurofibrillary tangles, neuropil threads, and dystrophic neurites in AD but not in aged-matched controls. These data not only provide further evidence for cell cycle aberrations in AD, but the cytoplasmic, rather than nuclear, localization of pMcm2 suggests an abnormal cellular distribution of this important replication factor in AD that may explain resultant cell cycle stasis and consequent neuronal degeneration.