Blog
About

3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Intraneuronal APP, not free Aβ peptides in 3xTg-AD mice: implications for tau versus Aβ-mediated Alzheimer neurodegeneration.

      The Journal of neuroscience : the official journal of the Society for Neuroscience

      metabolism, Alzheimer Disease, pathology, Amyloid beta-Peptides, physiology, Amyloid beta-Protein Precursor, Animals, Disease Models, Animal, Mice, Mice, Transgenic, Nerve Degeneration, Neurons, tau Proteins

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Alzheimer's disease (AD) is characterized by the accumulation of intraneuronal tau and extracellular amyloid-β (Aβ) peptide. A triple transgenic (Tg) mouse (3xTg-AD) was reported to develop Aβ plaques and tau inclusions as well as remarkable accumulations of intracellular Aβ that were suggested to be the initiators of AD pathogenesis. However, it was unclear whether the anti-Aβ antibodies were able to distinguish Aβ peptide from the same Aβ epitopes within the amyloid precursor protein (APP). To further elucidate the identity of the immunoreactive intraneuronal material in 3xTg-AD mice, we conducted immunohistochemical, biochemical, and ultrastructural studies using a well characterized panel of antibodies that distinguish Aβ within APP from cleaved Aβ peptides. We found that the intraneuronal material shared epitopes with full-length APP but not free Aβ. To demonstrate unequivocally that this intraneuronal material was not free Aβ peptide, we generated 3xTg-AD mice deficient for β-secretase (BACE), the protease required for Aβ generation from APP. In the absence of Aβ production, robust intraneuronal APP immunostaining was detected in the 3xTg-AD/BACE(-/-) mice. Finally, we found that the formation of tau lesions was not different between 3xTg-AD versus 3xTg-AD/BACE(-/-) mice, thereby demonstrating that tau pathology forms independently from Aβ peptide generation in this mouse model. Although we cannot corroborate the presence of intraneuronal Aβ peptide in 3xTg-AD mice, our findings warrant further study as to the role of aberrant APP accumulation in this unique model of AD.

          Related collections

          Author and article information

          Journal
          21613482
          3118598
          10.1523/JNEUROSCI.6637-10.2011

          Comments

          Comment on this article