A-β Related Pathogenesis of AD Progress of Its Targeted Therapy

Authors

  • Yunjuan Xie

DOI:

https://doi.org/10.61173/ewtnjq54

Keywords:

Alzheimer’s disease, beta-amyloid protein, Monoclonal antibody, Inhibitors, Therapeutic vaccine, APP

Abstract

Alzheimer’s disease is a common type of dementia in people 65 years of age and older. Tens of millions of people worldwide are living with AD, and the number continues to grow. To date, there are several hypotheses about the pathogenesis of AD, the most widely studied of which is related to the accumulation of Aβ. Currently, there are five drugs in clinical treatment, most of which are inhibitors, as well as monoclonal antibody drugs such as Aducanumab that target Aβ. These drugs can effectively reduce the accumulation of Aβ. However, these drugs have significant side effects and are generally significantly reduced by the end of AD symptoms. This review will summarize the pathogenesis of AD related to Aβ, such as APP and neuroinflammation. This article will also discuss the progress and problems of existing Aβ-based therapies. In addition, this paper will also compare Aβ and Tau proteins to explore better AD treatment methods. These are the basis for further study of the pathogenesis of AD related to Aβ and the development of drugs based on it. Future studies could focus on the direction of immunotherapy targeting Aβ, and apply these drugs to therapies targeting Tau protein.

References

achieved good clinical results [17]. So treatments that can interfere with the interaction between the Aβ and Tau proteins need to be investigated. For example, the production [1] Chen G, Xu T, Yan Y, et al. Amyloid beta: structure, of GSK-3β and CDK-5 inhibitors induced by the hyper- Biology and structure-based Therapeutic Development. Acta phosphorylation of Tau protein induced by Aβ activation Pharmacologica Sinica, 2017, 38(9): 1205–1235. can be studied. However, until now, no inhibitor has been [2] Pardo-Moreno T, González-Acedo A, Rivas-Domínguez A, proposed that can inhibit both Aβ induction and Tau hy- et al. Therapeutic Approach to Alzheimer’s Disease: Current perphosphorylation [17]. This may be due to the fact that Treatments and New Perspectives. Pharmaceutics, 2022, 14(6): pathways containing multiple targets cannot be inhibited 1117. simultaneously by inhibitors. [3] Kocahan S, Doğan Z. Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, 6. Conclusions N-methyl-D-aspartate Receptors, Tau Protein and Other Risk So far, there are many hypotheses about the pathogenesis Factors. Clinical Psychopharmacology and Neuroscience, 2017, of AD related to Aβ, such as APP, mitochondrial disorders, 15(1): 1–8. and neuroinflammation. Because of these assumptions, Aβ [4] Zhang Y, Chen H, Li R, et al. Amyloid β-based therapy for is considered to be one of the most important factors in Alzheimer’s disease: challenges, successes and future. Signal the development of AD, so it is often used as an important Transduction and Targeted Therapy, 2023, 8(1): 1–26. target in treatment programs. However, due to the enor- [5] Karran E, De Strooper B. The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics. Nature

Reviews Drug Discovery, 2022, 21. www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers- [6] Hampel H, Hardy J, Blennow K, et al. The Amyloid-β disease-treated. Pathway in Alzheimer’s Disease. Molecular Psychiatry, 2021, [13] Silvestro S, Valeri A, Mazzon E. Aducanumab and Its 26(10). Effects on Tau Pathology: Is This the Turning Point of Amyloid [7] Sheppard O, Coleman M. Alzheimer’s Disease: Etiology, Hypothesis?. International Journal of Molecular Sciences, 2022, Neuropathology and Pathogenesis. PubMed, 2020[2024-08-31]. 23(4): 2011. https://www.ncbi.nlm.nih.gov/books/NBK566126/. [14] Nordvall G, Lundkvist J, Sandin J. Gamma-secretase [8] Zhang Y, Thompson R, Zhang H, et al. APP processing in modulators: a promising route for the treatment of Alzheimer’s Alzheimer’s disease. Molecular Brain, 2011, 4(1): 3. disease. Frontiers in Molecular Neuroscience, 2023, 16: [9] Ionescu-Tucker A, Cotman C W. Emerging roles of oxidative 1279740. stress in brain aging and Alzheimer’s disease. Neurobiology of [15] Vicidomini C, Borbone N, Roviello V, et al. Summary of Aging, 2021, 107: 86-95. the Current Status of DNA Vaccination for Alzheimer Disease. [10] Rather M A, Khan A, Alshahrani S, et al. Inflammation and Vaccines, 2023, 11(11): 1706. Alzheimer’s Disease: Mechanisms and Therapeutic Implications [16] Walsh S, Merrick R, Milne R, et al. Considering challenges by Natural Products. Mediators of Inflammation, 2021: 1–21. for the new Alzheimer’s drugs: Clinical, population, and health [11] Zhang Y, Chen H, Li R, et al. Amyloid β-based therapy for system perspectives. Alzheimer’s & Dementia, 2024. Alzheimer’s disease: challenges, successes and future. Signal [17] Zhang H, Wei W, Zhao M, et al. Interaction between Aβ and Transduction and Targeted Therapy, 2023, 8(1): 1–26. Tau in the Pathogenesis of Alzheimer’s Disease. International [12] National Institute on Aging. How is Alzheimer’s disease Journal of Biological Sciences, 2021, 17(9): 2181–2192. treated?. National Institute on Aging, 2023[2024-08-31]. https://

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Published

2024-10-29