| First Author | Winton MJ | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 21 | Pages | 7691-9 |
| PubMed ID | 21613482 | Mgi Jnum | J:173328 |
| Mgi Id | MGI:5013869 | Doi | 10.1523/JNEUROSCI.6637-10.2011 |
| Citation | Winton MJ, et al. (2011) Intraneuronal APP, Not Free A{beta} Peptides in 3xTg-AD Mice: Implications for Tau versus A{beta}-Mediated Alzheimer Neurodegeneration. (RETRACTED: J Neurosci 2015 Feb 25;35(8):3724). J Neurosci 31(21):7691-9 |
| abstractText | Alzheimer's disease (AD) is characterized by the accumulation of intraneuronal tau and extracellular amyloid-beta (Abeta) peptide. A triple transgenic (Tg) mouse (3xTg-AD) was reported to develop Abeta plaques and tau inclusions as well as remarkable accumulations of intracellular Abeta that were suggested to be the initiators of AD pathogenesis. However, it was unclear whether the anti-Abeta antibodies were able to distinguish Abeta peptide from the same Abeta 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 Abeta within APP from cleaved Abeta peptides. We found that the intraneuronal material shared epitopes with full-length APP but not free Abeta. To demonstrate unequivocally that this intraneuronal material was not free Abeta peptide, we generated 3xTg-AD mice deficient for beta-secretase (BACE), the protease required for Abeta generation from APP. In the absence of Abeta 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 Abeta peptide generation in this mouse model. Although we cannot corroborate the presence of intraneuronal Abeta peptide in 3xTg-AD mice, our findings warrant further study as to the role of aberrant APP accumulation in this unique model of AD. |
