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Visualizing Aβ deposits in live young AD model mice with a simple red/near-infrared-fluorescent AIEgen

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Abstract

Precise and early detection of β-amyloid (Aβ) deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease (AD). Optical imaging stands out to be a promising technique for such a task; however, it still remains a big challenge, due to the lack of high-performance imaging contrast agent. Restricted by poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, as well as the aggregation-caused quenching effect, the widely used gold-standard probes cannot be used for early in-vivo imaging of Aβ deposits. Herein, we integrate the Aβ deposits-favored geometry, amphiphilic and zwitterionic molecular structure, extended D-π-A electronic structure, and 3D conformation into one molecule, facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to Aβ deposits, good BBB penetrability, bright red/near-infrared fluorescence, low interference from autofluorescence, aggregation-induced emission (AIE) feature, high signal-to-noise ratio (SNR), and high contrast. In-vitro, ex-vivo, and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to Aβ deposits identification. Noteworthily, AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed Aβ deposits in AD model mice as young as 4-month-old APP/PS1 mice, the youngest having Aβ deposits. Moreover, the present probe could clearly reveal the increase and enlargement of Aβ deposits as the mice grow. Therefore, AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.

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References

  1. Panza F, Lozupone M, Logroscino G, Imbimbo BP. Nat Rev Neurol, 2019, 15: 73–88

    Article  PubMed  Google Scholar 

  2. Zhu S, Wang J, Zhang Y, He J, Kong J, Wang JF, Li XM. CNS Neurosci Ther, 2017, 23: 310–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fan DY, Wang YJ. Neurosci Bull, 2020, 36: 195–197

    Article  CAS  Google Scholar 

  4. Jagust WJ, Landau SM. Neurology, 2021, 96: e1347–e1357

    Article  CAS  PubMed  Google Scholar 

  5. van Harten AC, Wiste HJ, Weigand SD, Mielke MM, Kremers WK, Eichenlaub U, Dyer RB, Algeciras-Schimnich A, Knopman DS, Jack CR, Petersen RC. Alzheimers & Dement, 2021, alz.12406

  6. Ma X, Wang Y, Hua J, Xu C, Yang T, Yuan J, Chen G, Guo Z, Wang X. Sci China Chem, 2020, 63: 73–82

    Article  CAS  Google Scholar 

  7. Aliyan A, Cook NP, Martí AA. Chem Rev, 2019, 119: 11819–11856

    Article  CAS  PubMed  Google Scholar 

  8. Jun YW, Cho SW, Jung J, Huh Y, Kim YS, Kim D, Ahn KH. ACS Cent Sci, 2019, 5: 209–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M, Beach TG, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Catafau AM, Stephens AW, Mueller A, Koglin N, Hoffmann A, Roth K, Reininger C, Schulz-Schaeffer WJ. Alzheimers & Dement, 2015, 11: 964–974

    Article  Google Scholar 

  10. Cai J, Yi P, Miao Y, Liu J, Hu Y, Liu Q, Feng Y, Chen H, Li L. ACS Appl Mater Interfaces, 2020, 12: 26812–26821

    Article  CAS  PubMed  Google Scholar 

  11. Zhao DS, Chen YX, Liu Q, Zhao YF, Li YM. Sci China Chem, 2011, 55: 112–117

    Article  Google Scholar 

  12. Hatai J, Motiei L, Margulies D. J Am Chem Soc, 2017, 139: 2136–2139

    Article  CAS  PubMed  Google Scholar 

  13. Staderini M, Martín MA, Bolognesi ML, Menéndez JC. Chem Soc Rev, 2015, 44: 1807–1819

    Article  CAS  PubMed  Google Scholar 

  14. Shin J, Verwilst P, Choi H, Kang S, Han J, Kim NH, Choi JG, Oh MS, Hwang JS, Kim D, Mook-Jung I, Kim JS. Angew Chem Int Ed, 2019, 58: 5648–5652

    Article  CAS  Google Scholar 

  15. Law ASY, Lee LCC, Yeung MCL, Lo KKW, Yam VWW. J Am Chem Soc, 2019, 141: 18570–18577

    Article  CAS  PubMed  Google Scholar 

  16. Fu W, Yan C, Guo Z, Zhang J, Zhang H, Tian H, Zhu WH. J Am Chem Soc, 2019, 141: 3171–3177

    Article  CAS  PubMed  Google Scholar 

  17. Cui M, Ono M, Watanabe H, Kimura H, Liu B, Saji H. J Am Chem Soc, 2014, 136: 3388–3394

    Article  CAS  PubMed  Google Scholar 

  18. Zhou K, Bai H, Feng L, Dai J, Cui M. Anal Chem, 2017, 89: 9432–9437

    Article  CAS  PubMed  Google Scholar 

  19. Peng C, Wang X, Li Y, Li HW, Wong MS. J Mater Chem B, 2019, 7: 1986–1995

    Article  CAS  PubMed  Google Scholar 

  20. Yan JW, Zhu JY, Zhou KX, Wang JS, Tan HY, Xu ZY, Chen SB, Lu YT, Cui MC, Zhang L. Chem Commun, 2017, 53: 9910–9913

    Article  CAS  Google Scholar 

  21. Fu H, Peng C, Liang Z, Dai J, Liu B, Cui M. Chem Commun, 2016, 52: 12745–12748

    Article  CAS  Google Scholar 

  22. Cheng Y, Zhu B, Deng Y, Zhang Z. Anal Chem, 2015, 87: 4781–4787

    Article  CAS  PubMed  Google Scholar 

  23. Rajasekhar K, Narayanaswamy N, Murugan NA, Kuang G, Ågren H, Govindaraju T. Sci Rep, 2016, 6: 23668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Diner I, Dooyema J, Gearing M, Walker LC, Seyfried NT. Bioconj Chem, 2017, 28: 2627–2637

    Article  CAS  Google Scholar 

  25. Liu B, Shen H, Hao Y, Zhu X, Li S, Huang Y, Qu P, Xu M. Anal Chem, 2018, 90: 12449–12455

    Article  CAS  PubMed  Google Scholar 

  26. Lei L, Geng R, Xu Z, Dang Y, Hu X, Li L, Geng P, Tian Y, Zhang W. Anal Chem, 2019, 91: 8129–8136

    Article  CAS  PubMed  Google Scholar 

  27. Wang YL, Fan C, Xin B, Zhang JP, Luo T, Chen ZQ, Zhou QY, Yu Q, Li XN, Huang ZL, Li C, Zhu MQ, Tang BZ. Mater Chem Front, 2018, 2: 1554–1562

    Article  CAS  Google Scholar 

  28. Dou WT, Zhang JJ, Li Q, Guo Z, Zhu W, Chen GR, Zhang HY, He XP. ChemBioChem, 2019, 20: 1856–1860

    Article  CAS  PubMed  Google Scholar 

  29. Tan H, Zhou K, Yan J, Sun H, Pistolozzi M, Cui M, Zhang L. Sens Actuat B-Chem, 2019, 298: 126903

    Article  CAS  Google Scholar 

  30. Yang Y, Li S, Zhang Q, Kuang Y, Qin A, Gao M, Li F, Tang BZ. J Mater Chem B, 2019, 7: 2434–2441

    Article  CAS  PubMed  Google Scholar 

  31. Luo J, Xie Z, Lam JWY, Cheng L, Tang BZ, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu D. Chem Commun, 2001, 1740–1741

  32. Hong Y, Meng L, Chen S, Leung CWT, Da LT, Faisal M, Silva DA, Liu J, Lam JWY, Huang X, Tang BZ. J Am Chem Soc, 2012, 134: 1680–1689

    Article  CAS  PubMed  Google Scholar 

  33. Kumar M, Hong Y, Thorn DC, Ecroyd H, Carver JA. Anal Chem, 2017, 89: 9322–9329

    Article  CAS  PubMed  Google Scholar 

  34. Ou H, Dai S, Liu R, Ding D. Sci China Chem, 2019, 62: 929–932

    Article  CAS  Google Scholar 

  35. Ni X, Zhang X, Duan X, Zheng HL, Xue XS, Ding D. Nano Lett, 2019, 19: 318–330

    Article  CAS  PubMed  Google Scholar 

  36. Mei J, Huang Y, Tian H. ACS Appl Mater Interfaces, 2018, 10: 12217–12261

    Article  CAS  PubMed  Google Scholar 

  37. Gao Z, Gao H, Zheng D, Xu T, Chen Y, Liang C, Wang L, Ding D, Yang Z. Sci China Chem, 2020, 63: 398–403

    Article  CAS  Google Scholar 

  38. Li J, Gao H, Liu R, Chen C, Zeng S, Liu Q, Ding D. Sci China Chem, 2020, 63: 1428–1434

    Article  CAS  Google Scholar 

  39. Yu CYY, Zhang W, Kwok RTK, Leung CWT, Lam JWY, Tang BZ. J Mater Chem B, 2016, 4: 2614–2619

    Article  CAS  PubMed  Google Scholar 

  40. Donabedian PL, Pham TK, Whitten DG, Chi EY. ACS Chem Neurosci, 2015, 6: 1526–1535

    Article  CAS  PubMed  Google Scholar 

  41. Rahimi F, Maiti P, Bitan G. J Vis Exp, 2009, 23: e1071

    Google Scholar 

  42. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Jr. Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision A02. Wallingford CT: Gaussian, Inc., 2009

    Google Scholar 

  43. Lührs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, Döbeli H, Schubert D, Riek R. Proc Natl Acad Sci USA, 2005, 102: 17342–17347

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tomaselli S, Esposito V, Vangone P, van Nuland NAJ, Bonvin AMJJ, Guerrini R, Tancredi T, Temussi PA, Picone D. ChemBioChem, 2006, 7: 257–267

    Article  CAS  PubMed  Google Scholar 

  45. Protein Data Bank. A Structural View of Biology. http://www.rcsb.org/, accessed on 2021-08-10

  46. Sanner MF, Huey R, Dallakyan S, Carrillo C, Chan K, Coon S, Gillet A, Karnati S, Lindstrom W, Morris MG, Norledge B, Omelchenko A, Stoffler D, Tschinke V, Vareille G, Zhao Y. MGL Tools-1.5.7. Molecular Graphics Laboratory, The Scripps Research Institute, 1999–2011

  47. DeLano WL. The PyMOL molecular graphics system. Palo Alto: DeLano Scientific LLC, 2008

    Google Scholar 

  48. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R. J Neurosci, 2006, 26: 10129–10140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fu H, Cui M, Zhao L, Tu P, Zhou K, Dai J, Liu B. J Med Chem, 2015, 58: 6972–6983

    Article  CAS  PubMed  Google Scholar 

  50. Liu H, Qian C, Yang T, Wang Y, Luo J, Zhang C, Wang X, Wang X, Guo Z. Chem Sci, 2020, 11: 7158–7169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Sciences Foundation of China (21788102, 21875064, 81903545, 21604023, 21790361), Shanghai Science and Technology Commission Basic Project-Shanghai Natural Science Foundation (21ZR1417600), Shanghai Municipal Science and Technology Major Project (2018SHZDZX03), Programme of Introducing Talents of Discipline to Universities (B16017), Shanghai Science and Technology Committee (17520750100), Beijing New-Star Plan of Science and Technology (Z201100006820009), Shanghai Sailing Program (16YF1402200), and the Fundamental Research Funds for the Central Universities.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory for Advanced Materials, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Joint International Research Laboratory for Precision Chemistry and Molecular Engineering, Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science & Technology, Shanghai, 200237, China

    Yipu Wang, Xinyi Zhang, Da-Hui Qu & Ju Mei

  2. Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Dong Mei

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  1. Yipu Wang
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Correspondence to Ju Mei.

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Wang, Y., Mei, D., Zhang, X. et al. Visualizing Aβ deposits in live young AD model mice with a simple red/near-infrared-fluorescent AIEgen. Sci. China Chem. 65, 339–352 (2022). https://doi.org/10.1007/s11426-021-1113-0

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