Neurotoxicity Research

, Volume 21, Issue 2, pp 160–174

BACE1 Elevation is Involved in Amyloid Plaque Development in the Triple Transgenic Model of Alzheimer’s Disease: Differential Aβ Antibody Labeling of Early-Onset Axon Terminal Pathology

Authors

  • Yan Cai
    • Department of Human Anatomy and NeurobiologyCentral South University Xiangya School of Medicine
    • Department of AnatomySouthern Illinois University School of Medicine
    • Department of PhysiologySouthern Illinois University School of Medicine
  • Xue-Mei Zhang
    • Department of AnatomySouthern Illinois University School of Medicine
    • Department of Neurology, The Second Affiliated HospitalHarbin Medical University
  • Lauren N. Macklin
    • Department of PhysiologySouthern Illinois University School of Medicine
  • Huaibin Cai
    • Laboratory of NeurogeneticsNational Institute on Aging
  • Xue-Gang Luo
    • Department of Human Anatomy and NeurobiologyCentral South University Xiangya School of Medicine
  • Salvatore Oddo
    • Department of Physiology and The Barshop Institute for Longevity and Aging StudiesUniversity of Texas Health Science Center at San Antonio
  • Frank M. LaFerla
    • Department of Neurobiology and BehaviorUniversity of California, Irvine
  • Robert G. Struble
    • Center for Alzheimer’s diseaseSouthern Illinois University School of Medicine
  • Gregory M. Rose
    • Department of AnatomySouthern Illinois University School of Medicine
  • Peter R. Patrylo
    • Department of AnatomySouthern Illinois University School of Medicine
    • Department of PhysiologySouthern Illinois University School of Medicine
    • Department of Human Anatomy and NeurobiologyCentral South University Xiangya School of Medicine
    • Department of AnatomySouthern Illinois University School of Medicine
Article

DOI: 10.1007/s12640-011-9256-9

Cite this article as:
Cai, Y., Zhang, X., Macklin, L.N. et al. Neurotox Res (2012) 21: 160. doi:10.1007/s12640-011-9256-9

Abstract

β-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer’s disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. β-Amyloid (Aβ) deposition can manifest as compact and diffuse plaques; it is unclear why the same Aβ molecules aggregate in different patterns. Is there a basic cellular process governing Aβ plaque pathogenesis? We showed in some FAD mouse models that compact plaque formation is associated with a progressive axonal pathology inherent with increased expression of β-secretase (BACE1), the enzyme initiating the amyloidogenic processing of APP. A monoclonal Aβ antibody, 3D6, visualized distinct axon terminal labeling before plaque onset. The present study was set to understand BACE1 and axonal changes relative to diffuse plaque development and to further characterize the novel axonal Aβ antibody immunoreactivity (IR), using triple transgenic AD (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the forebrain in aged transgenics and were regionally associated with increased BACE1 labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon terminals occurred in young animals before plaque onset. These axonal elements were also co-labeled by other antibodies targeting the N-terminal and mid-region of Aβ domain and the C-terminal of APP, but not co-labeled by antibodies against the Aβ C-terminal and APP N-terminal. The results suggest that amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD mice, and that the early-onset axonal Aβ antibody IR in transgenic models of AD might relate to a cross-reactivity of putative APP β-carboxyl terminal fragments.

Keywords

Amyloid plaqueAxonal pathologySynaptoplasticityAgingDementia

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC 2011