被撤回的出版物: Intraneuronal APP, Not Free Aβ Peptides in 3xTg-AD Mice: Implications for Tau versus Aβ-Mediated Alzheimer Neurodegeneration (Retracted article. See vol. 35, pg. 3724, 2015)

Alzheimer's disease (AD) is characterized by the accumulation of intraneuronal tau and extracellular amyloid-beta (A beta) peptide. A triple transgenic (Tg) mouse (3xTg-AD) was reported to develop A beta plaques and tau inclusions as well as remarkable accumulations of intracellular A beta that were suggested to be the initiators of AD pathogenesis. However, it was unclear whether the anti-A beta antibodies were able to distinguish A beta peptide from the same A beta 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 A beta within APP from cleaved A beta peptides. We found that the intraneuronal material shared epitopes with full-length APP but not free A beta. To demonstrate unequivocally that this intraneuronal material was not free A beta peptide, we generated 3xTg-AD mice deficient for beta-secretase (BACE), the protease required for A beta generation from APP. In the absence of A beta 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 A beta peptide generation in this mouse model. Although we cannot corroborate the presence of intraneuronal A beta peptide in 3xTg-AD mice, our findings warrant further study as to the role of aberrant APP accumulation in this unique model of AD.