Meeting the Grand Challenges of Alzheimer's: Early Detection, Diagnostics, and Therapeutics
Alzheimer’s disease (AD), characterized by the problems of memory loss, thinking and cognitive behaviour is not only the most prevalent neurodegenerative dementia, but also the third most common cause of death among the elderly. Despite tremendous resources and effort being put on understanding the disease mechanism as well as developing diagnoses and treatments in the past two decades, the underlying cause of incurable AD is not fully understood yet. Therefore, there are unmet grand challenges in the aspects of early detection, diagnostics and therapeutics.
With the assembly of an interdisciplinary research team, we propose herein:
- To develop sensitive detection and accurate quantification of soluble Aβ oligomers as AD biomarkers, which could allow population-wide screening and early pre-clinical diagnoses of AD. Detection and quantification of AD biomarkers are informative and indispensable for preclinical AD diagnosis even before the presence of amyloid deposition, as early diagnosis of at-risk subjects allows preventive and delaying measures for the progression to AD.
- To develop Aβ-specific magnetic resonance imaging contrast agents as a powerful tool to detect, diagnose and monitor the disease’s status and progression. Development of a powerful imaging technique with molecular sensitivity for AD diagnosis is crucial to monitoring the disease’s progression and understanding the complex disease processes, as well as the evaluation of effectiveness of potential AD drugs.
- To develop multi-target, non-toxic and blood-brain barrier permeable cyanine compounds that serve as effective drug candidates for the intervention of AD. AD has a multifactorial pathoetiological origin. Current therapeutic approaches only offer limited remedies with only transient symptomatic benefits to patients, but without halting or reversing the progression of the disease. Development of multi-target drugs that act on two or more specific etiological targets of the disease would offer a better pathway towards the development of disease-modifying treatments.
- Collaborative Research Fund: Alzheimer's Disease: From Detection, Diagnostics to Therapeutics (Interview from the Research Grants Council, Hong Kong)
- Dual‐Modal NIR‐Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid‐β Species In Vivo (A video abstract invited by the journal Small)
- Newspaper reports on the AD research breakthrough locally and internationally
- C. Wang, X. Wang, H.-N. Chan, G. Liu, Z. Wang, H. W. Li, M. S. Wong Amyloid-β Oligomer-Targeted Gadolinium-Based NIR/MR Dual-Modal Theranostic Nanoprobe for Alzheimer’s Disease Adv. Func. Mater. 2020, 30, 1909529. (with inside cover) https://doi.org/10.1002/adfm.201909529
- C. Chen, D. Xu, Z.-H. Zhang, S.-Z. Jia, X.-C. Cao, Y.-B. Chen, G.-L. Song, M. S. Wong, H. W. Li Cognitive Improvement and Synaptic Deficit Attenuation by a Multifunctional Carbazole-Based Cyanine in AD Mice Model through Regulation of Ca2+/CaMKII/CREB Signaling Pathway Experimental Neurology 2020, 327, 113210. https://doi.org/10.1016/j.expneurol.2020.113210
- X. Wang, S.-L. Ho, C.-Y. Poon, T. Yan, H.-W. Li, M. S. Wong Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer’s Diseases Current Alzheimer Research 2019, 16, 836-842. DOI:10.2174/1567205016666190827123222
- H.-N. Chan, D. Xu, S.-L. Ho, D. He, M. S. Wong, H.-W. Li Highly Sensitive Quantification of Alzheimer’s Disease Biomarkers by Aptamer-Assisted Amplification Theranostics 2019, 9(10), 2939 – 2949. doi: 10.7150/thno.29232
- C. Peng, X. Wang, Y. Li, H.-W. Li, M. S. Wong Versatile Fluorescent Probes for Near-Infrared Imaging of Amyloid-β Species in Alzheimer’s Disease Mouse Model J. Mater. Chem. B, 2019, 7, 1986 – 1995. (Hot paper) DOI: 10.1039/c9tb00161a
- Y. Li, D. Xu, H.-N. Chan, C.-Y. Poon, S.-L. Ho, H.-W. Li, M. S. Wong Dual-Modal NIR-Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid-β Species in Vivo Small, 2018, 14 (28), 1800901. (with Frontispiece cover) Video Abstract at: https://youtu.be/FzfaLXcJ2Pkhttps://doi.org/10.1002/smll.201800901
- Y. Li, C. Chen, D. Xu, C.-Y. Poon, S.-L. Ho, R. Zheng, Q. Liu, G. L. Song, H.-W. Li, M. S. Wong Effective Theranostic Cyanine for Imaging of Amyloid Species in vivo and Cognitive Improvements in Mouse Model ACS Omega 2018, 3 (6), 6812–6819. (25 JUNE) DOI: 10.1021/acsomega.8b00475
- Y. Li, D. Xu, A. Sun, S.-L. Ho, C.-Y. Poon, H.-N. Chan, O. T. W. Ng, K. K. L. Yung, H. Yan, H.-W. Li, M. S. Wong, Fluoro-Substituted Cyanine for Reliable in vivo Labelling of Amyloid-β Oligomers and Neuroprotection against Amyloid-β Induced Toxicity Chem. Sci. 2017, 8, 8279 - 8284. YouTube link at https://www.youtube.com/watch?v=6Axwtdlo-wQDOI: 10.1039/c7sc03974c
- H.-N. Chan, D. Xu, S.-L. Ho, M. S. Wong, H.-W. Li Ultra-sensitive Detection of Protein Biomarkers for Diagnosis of Alzheimer’s Disease Chem. Sci. 2017, 8, 4012-4018. YouTube link at https://www.youtube.com/watch?v=6Axwtdlo-wQ DOI: 10.1039/c6sc05615f
- Y. Li, D. Xu, S.-L. Ho, H.-W. Li, R. Yang, M. S. Wong A Theranostic Agent for in Vivo Near-Infrared Imaging of β-Amyloid Species and Inhibition of β-Amyloid Aggregation Biomaterials 2016, 94, 84-92. http://dx.doi.org/10.1016/j.biomaterials.2016.03.047
- S.-L. Ho, C.-Y. Poon, C. Lin, T. Yan, D.W.J. Kwong, K.K.L. Yung, M.S. Wong, Z. Bian, H.-W. Li Inhibition of β-Amyloid Aggregation by Albiflorin, Aloeemodin and Neohesperidin and their Neuroprotective Effect on Primary Hippocampal Cells Against β-Amyloid Induced Toxicity Curr. Alzheimer Res. 2015, 12, 424-433. doi: 10.2174/1567205012666150504144919.
- W. Yang, Y. Wong, O.T.W. Ng, L.-P. Bai, D.W.J. Kwong, Y. Ke, Z.-H. Jiang, H.-W. Li, K.K.L. Yung, M.S. Wong, Inhibition of Beta-Amyloid Peptide Aggregation by Multifunctional Carbazole-Based Fluorophores Angew. Chem. Int. Ed. 2012, 51, 1804-1810. (with Frontispiece cover) http://dx.doi.org/10.1002/anie.201104150.
- S.-L. Ho, H.-N. Chan, D. Xu, H.W. Li, R.M.S. Wong, “Magnetic Platform for Direct and Multiplex Immune-Based Detection of Trace Amount of Protein Biomarkers” US non-provisional patent application No. 15/276,811 (Notice of allowance was received on June1, 2020)
- Y. Li, D. Xu, S.-L. Ho, C.-Y. Poon, H.-N. Chan, H.W. Li, R.M.S. Wong, “Imaging Beta-Amyloid Peptides Aggregation” US Patent No.: US 9795694 B2 (2017). (granted on 24 Oct 2017)
- 杨王贵，黄怡，吴芷桦，李红荣，翁建霖，邝维正，黄文成“β淀粉样肽的成像及β淀粉样肽的聚集的抑制”，Chinese Patent: CN 102743769 B (2016) (granted on 2 Nov 2016)
- L. Guo, D. Xu, S.-L. Ho, C.-Y. Poon, O. T. W. Ng, H.W. Li, K.K.L. Yung, D.W.J. Kwong, R.M.S. Wong, “Imaging Beta-Amyloid Peptides and Inhibition of Beta-Amyloid Peptide Aggregation”, US Patent No.: US 9403794 B2 (2016). (granted on 2 Aug 2016)
- L. Guo, D. Xu, S.-L. Ho, C.-Y. Poon, O. T. W. Ng, H.W. Li, K.K.L. Yung, D.W.J. Kwong, R.M.S. Wong, “Imaging Beta-Amyloid Peptides and Inhibition of Beta-Amyloid Peptide Aggregation”, US Patent No.: US 9255933 B2 (2016). (granted on 9 Feb 2016)
- W. Yang, Y. Wong, O.T.W. Ng, H.W. Li, K.K.L. Yung, D.W.J. Kwong, R.M.S. Wong, “Imaging Beta-Amyloid Peptides and Inhibition of Beta-Amyloid Peptide Aggregation”, US Patent No.: US 9156814 B2 (2015). (granted on 13 Oct 2015)