Research Report Aberrant localization of importin α1 in hippocampal neurons in Alzheimer disease Hyoung-gon Lee a, ⁎ , Masumi Ueda a , Yoichi Miyamoto b , Yoshihiro Yoneda b , George Perry a,c , Mark A. Smith a, ⁎ , Xiongwei Zhu a a Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA b Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan c College of Sciences, University of Texas at San Antonio, San Antonio, Texas 78249, USA ARTICLE INFO ABSTRACT Article history: Accepted 24 September 2006 Available online 27 October 2006 Since many nuclear proteins are ectopically localized in the cytoplasm in the vulnerable neurons in Alzheimer disease (AD), we speculated that there is failure of the cytoplasmic- nuclear transport machinery in AD. In support of this notion, we found that importin α1, an essential component of cytoplasmic-nuclear transport, is abnormally accumulated in Hirano bodies in vulnerable hippocampal neurons in AD. These data suggest a hindrance in importin-mediated cytoplasmic-nuclear transport in AD. © 2006 Elsevier B.V. All rights reserved. Keywords: Alzheimer disease Cytoplasmic-nuclear transport Hirano body Importin Abbreviations: AD, Alzheimer disease APTX, aprataxin DAB, 3-3′-diaminobenzidine GVD, granular vacuolar degeneration NFT, neurofibrillary tangles NGS, normal goat serum NLS, nuclear localization signal NPC, nuclear pore complex NTF2, nuclear transport factor 2 PHF, paired helical filaments TBS, Tris-buffered saline 1. Introduction The specific and appropriate localization of proteins after translation is necessary for their proper activity. For nuclear proteins produced in the cytoplasm, transport from the cytoplasm to the nucleus is essential for their functions inside the nucleus. In Alzheimer disease (AD), there is aberrant localization of nuclear proteins involved in cell cycle activation BRAIN RESEARCH 1124 (2006) 1 – 4 ⁎ Corresponding authors. Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. Fax: +1 216 368 8964. E-mail addresses: hyoung-gon.lee@case.edu (H. Lee), mark.smith@case.edu (M.A. Smith). 0006-8993/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.09.084 available at www.sciencedirect.com www.elsevier.com/locate/brainres