Tau pathogenesis is promoted by Aβ1-42 but not Aβ1-40

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• 作者：Xiaoyan Hu ; Xiaoling Li ; Mingrui Zhao ; Andrew Gottesdiener…
• 关键词：Aβ1-2 ; Aβ1-0 ; tau ; Alzheimer’s disease ; Aggregation ; Phosphorylation ; Cleavage
• 刊名：Molecular Neurodegeneration
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：2,541 KB
• 参考文献：1. Gotz, J, Chen, F, van Dorpe, J, Nitsch, RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293: pp. 1491-1495 CrossRef
  2. Lewis, J, Dickson, DW, Lin, WL, Chisholm, L, Corral, A, Jones, G, Yen, SH, Sahara, N, Skipper, L, Yager, D, Eckman, C, Hardy, J, Hutton, M, McGowan, E (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293: pp. 1487-1491 CrossRef
  3. Jin, M, Shepardson, N, Yang, T, Chen, G, Walsh, D, Selkoe, DJ (2011) Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci U S A 108: pp. 5819-5824 CrossRef
  4. McGowan, E, Pickford, F, Kim, J, Onstead, L, Eriksen, J, Yu, C, Skipper, L, Murphy, MP, Beard, J, Das, P, Jansen, K, Delucia, M, Lin, WL, Dolios, G, Wang, R, Eckman, CB, Dickson, DW, Hutton, M, Hardy, J, Golde, T (2005) Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47: pp. 191-199 CrossRef
  5. Kim, J, Onstead, L, Randle, S, Price, R, Smithson, L, Zwizinski, C, Dickson, DW, Golde, T, McGowan, E (2007) Abeta40 inhibits amyloid deposition in vivo. J Neurosci 27: pp. 627-633 CrossRef
  6. Zou, K, Yamaguchi, H, Akatsu, H, Sakamoto, T, Ko, M, Mizoguchi, K, Gong, JS, Yu, W, Yamamoto, T, Kosaka, K, Yanagisawa, K, Michikawa, M (2007) Angiotensin-converting enzyme converts amyloid beta-protein 1-2 (Abeta(1-2)) to Abeta(1-0), and its inhibition enhances brain Abeta deposition. J Neurosci 27: pp. 8628-8635 CrossRef
  7. Murray, MM, Bernstein, SL, Nyugen, V, Condron, MM, Teplow, DB, Bowers, MT (2009) Amyloid beta protein: Abeta40 inhibits Abeta42 oligomerization. J Am Chem Soc 131: pp. 6316-6317 CrossRef
  8. Murray, MM, Krone, MG, Bernstein, SL, Baumketner, A, Condron, MM, Lazo, ND, Teplow, DB, Wyttenbach, T, Shea, JE, Bowers, MT (2009) Amyloid beta-protein: experiment and theory on the 21-0 fragment. J Phys Chem B 113: pp. 6041-6046 CrossRef
  9. De Felice, FG, Wu, D, Lambert, MP, Fernandez, SJ, Velasco, PT, Lacor, PN, Bigio, EH, Jerecic, J, Acton, PJ, Shughrue, PJ, Chen-Dodson, E, Kinney, GG, Klein, WL (2008) Alzheimer’s disease-type neuronal tau hyperphosphorylation induced by A beta oligomers. Neurobiol Aging 29: pp. 1334-1347 CrossRef
  10. Biernat, J, Gustke, N, Drewes, G, Mandelkow, EM, Mandelkow, E (1993) Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron 11: pp. 153-163 CrossRef
  11. Harada, J, Sugimoto, M (1999) Activation of caspase-3 in beta-amyloid-induced apoptosis of cultured rat cortical neurons. Brain Res 842: pp. 311-323 CrossRef
  12. Schwabe, T, Bainton, RJ, Fetter, RD, Heberlein, U, Gaul, U (2005) GPCR signaling is required for blood–brain barrier formation in drosophila. Cell 123: pp. 133-144 CrossRef
  13. Yoshiyama, Y, Higuchi, M, Zhang, B, Huang, SM, Iwata, N, Saido, TC, Maeda, J, Suhara, T, Trojanowski, JQ, Lee, VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53: pp. 337-351 CrossRef
  14. Wang, X, Michaelis, EK (2010) Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2: pp. 12
  15. Frost, B, Jacks, RL, Diamond, MI (2009)
• 刊物主题：Neurosciences; Neurology; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1750-1326

文摘

Background The relationship between the pathogenic amyloid β-peptide species Aβ1-2 and tau pathology has been well studied and suggests that Aβ1-2 can accelerate tau pathology in vitro and in vivo. The manners if any in which Aβ1-0 interacts with tau remains poorly understood. In order to answer this question, we used cell-based system, transgenic fly and transgenic mice as models to study the interaction between Aβ1-2 and Aβ1-0. Results In our established cellular model, live cell imaging (using confocal microscopy) combined with biochemical data showed that exposure to Aβ1-2 induced cleavage, phosphorylation and aggregation of wild-type/full length tau while exposure to Aβ1-0 didn’t. Functional studies with Aβ1-0 were carried out in tau-GFP transgenic flies and showed that Aβ1-2, as previously reported, disrupted cytoskeletal structure while Aβ1-0 had no effect at same dose. To further explore how Aβ1-0 affects tau pathology in vivo, P301S mice (tau transgenic mice) were injected intracerebrally with either Aβ1-2 or Aβ1-0. We found that treatment with Aβ1-2 induced tau phosphorylation, cleavage and aggregation of tau in P301S mice. By contrast, Aβ1-0 injection didn’t alter total tau, phospho-tau (recognized by PHF-1) or cleavage of tau, but interestingly, phosphorylation at Ser262 was shown to be significantly decreased after direct inject of Aβ1-0 into the entorhinal cortex of P301S mice. Conclusions These results demonstrate that Aβ1-0 plays different role in tau pathogenesis compared to Aβ1-2. Aβ1-0 may have a protective role in tau pathogenesis by reducing phosphorylation at Ser262, which has been shown to be neurotoxic.