Study on Chemical Insights into Alzheimer’s Disease: Amyloid Beta and Tau Protein Interactions

Year : 2025 | Volume : 02 | Issue : 01 | Page : 37 46
    By

    Dhamodharan P,

Abstract

Background: Alzheimers disease (AD) is the most prevalent form of dementia, affecting millions of individuals worldwide and posing significant challenges to healthcare systems. The disease is characterized by a gradual decline in cognitive functions, particularly memory, reasoning, and the ability to perform daily activities. Aim & objective: To study chemical insights in alzheimers disease, especially amyloid beta and tau protein interactions Results & discussion: The results of this review highlight several key findings regarding the molecular mechanisms involved in Alzheimers disease (AD) and their implications for understanding the diseases progression and potential therapeutic targets. It discussed these Amyloid-Beta and Tau Protein Interactions, Role of Advanced Glycation End Products (AGEs), Neuroinflammation and Oxidative Stress, Genetic and Environmental Risk Factors, and Therapeutic Implications. Conclusion: The Biochemical mechanisms underlying Alzheimers disease (AD), focusing on the interactions between amyloid-beta (Aβ) and tau proteins, which are central to the diseases pathogenesis. It highlights the complex interplay of genetic and environmental risk factors contributing to AD and also emphasizes the need for ongoing research to develop effective therapeutic strategies targeting these molecular pathways.

Keywords: Alzheimers disease, amyloid-beta, tau protein, neuroinflammation, advanced glycation end products, RAGE, neurodegeneration.

[This article belongs to International Journal of Brain Sciences ]

How to cite this article:
Dhamodharan P. Study on Chemical Insights into Alzheimer’s Disease: Amyloid Beta and Tau Protein Interactions. International Journal of Brain Sciences. 2025; 02(01):37-46.
How to cite this URL:
Dhamodharan P. Study on Chemical Insights into Alzheimer’s Disease: Amyloid Beta and Tau Protein Interactions. International Journal of Brain Sciences. 2025; 02(01):37-46. Available from: https://journals.stmjournals.com/ijbs/article=2025/view=208170


References

1. Alzheimer’s Association. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement.
2018;14:367–429.
2. Ulery PG, Strickland DK. LRP in Alzheimer’s disease: Friend or foe? J Clin Investig.
2000;106:1077–9.
3. Sabbagh MN. FDA Position Statement Early Alzheimer’s Disease: Developing Drugs for
Treatment, Guidance for Industry. Amsterdam: Elsevier; 2019. p. 13–19.
4. Menendez-Gonzalez M, Padilla-Zambrano HS, Alvarez G, Capetillo-Zarate E, Tomas-Zapico C,
Costa A. Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s
Disease. Front Aging Neurosci. 2018;10:100.
5. Lee LL. Discovery of amyloid-beta aggregation inhibitors using an engineered assay for
intracellular protein folding and solubility. Protein Sci. 2009;18:277–86.
6. Deane R, Sagare A, Zlokovic BV. The role of the Cell Surface LRP and Soluble LRP in Blood-
Brain Barrier Aβ Clearance in Alzheimer’s Disease. Curr Pharm Des. 2008;14:1601–5.
7. Lue LF, Walker DG, Brachova L, Beach TG, Rogers J, Schmidt AM, et al. Involvement of
microglial receptor for advanced glycation end products (RAGE) in Alzheimer’s disease:
Identification of a cellular activation mechanism. Exp Neurol. 2001;171:29–45.
8. Deane RJ. Is RAGE still a therapeutic target for Alzheimer’s disease? Future Med Chem.
2012;4:915–25.
9. Dhananjayan K, Forbes J, Munch G. Advanced Glycation, Diabetes, and Dementia. In: Type 2
Diabetes and Dementia. Cambridge: Academic Press; 2018. p. 169–93.
10. Saleh A, Smith DR, Tessler L, Mateo AR, Martens C, Schartner E, et al. Receptor for advanced
glycation end-products (RAGE) activates divergent signalling pathways to augment neurite
outgrowth of adult sensory neurons. Exp Neurol. 2013;249:149–59.
11. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, et al. RAGE mediates
amyloid-beta peptide transport across the blood-brain barrier and accumulation in the
brain. Structure. 2011;19:722–32.
12. Koch M. Structural basis for ligand recognition and activation of RAGE. Structure.
2010;18:1342–52.
13. Haupt C, Bereza M, Kumar ST, Kieninger B, Morgado I, Hortschansky P, et al. Pattern
recognition with a fibril-specific antibody fragment reveals the surface variability of natural
amyloid fibril. J Mol Biol. 2011;408:529–40.
14. Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, et al. Advanced glycation end product
recognition by the receptor for AGEs. Structure. 2011;19:722–32.
15. Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, et al. Advanced glycation
endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol Aging.
2011;32:763–77.
16. Loske C, Gerdemann A, Schell W, Wycislo M, Schinzel R, Palm D, et al. Transition metal-
mediated glycoxidation accelerates cross-linking of beta-amyloid peptide. Eur J Biochem.
2000;267:4171–8.
17. World Health Organization. The Top 10 Causes of Death. 2018. Available from:
https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death
18. World Health Organization and Alzheimer’s Disease International. Dementia: a Public Health
Priority. Geneva: World Health Organization; 2012. ISBN 978-92-4-156445-8.
19. Alzheimer’s Disease International. World Alzheimer Report 2018. London; 2018. Available
from: https://www.alz.co.uk/research/world-report-2018
20. McGurran H, Glenn JM, Madero EN, Bott NT. Prevention and treatment of Alzheimer’s
disease: biological mechanisms of exercise. J Alzheimers Dis. 2019;69:311–38.
21. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, et al. The P2Y12 receptor
regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006;9:1512–9.

22. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic
reactive astrocytes are induced by activated microglia. Nature. 2017;541:481–7.
23. Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, et al. Dual microglia
effects on blood-brain barrier permeability induced by systemic inflammation. Nat Commun.
2019;10:5816.
24. Liu F, Cheng X, Zhong S, Liu C, Jolkkonen J, Zhang X, et al. Communications between
peripheral and the brain-resident immune system in neuronal regeneration after stroke.
Front Immunol. 2020;11:1931.
25. Jurcau A, Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion
injuries: From pathophysiology to therapeutic strategies. Int J Mol Sci. 2021;23:14.
26. Ransohoff RM. A polarizing question: Do M1 and M2 microglia exist? Nat Neurosci.
2016;19:987–91.
27. Spittau B. Aging microglia—Phenotypes, functions and implications for age-related
neurodegenerative diseases. Front Aging Neurosci. 2017;9:194.
28. Haas RH. Mitochondrial dysfunction in ageing and diseases of ageing. Biology. 2019;8:48.
29. Picca A, Lezza AMS, Leeuwenburgh C, Pesce V, Calvani R, Landi F, et al. Fueling inflammation
through mitochondrial dysfunction: Mechanisms and molecular targets. Int J Mol Sci.
2017;18:933.
30. Barbosa MC, Grosso RA, Fader CM. Hallmarks of ageing: An autophagic perspective. Front
Endocrinol. 2019;9:790.
31. Hegde AN, Smith SG, Duke LM, Pourquoi A, Vaz S. Perturbations of ubiquitin-
proteasome-mediated proteolysis in ageing and Alzheimer’s disease. Front Aging
Neurosci. 2019;11:324.
32. Chen G, Yung R. Meta-inflammaging at the crossroads of geroscience. Aging Med.
2019;2(3):157–61.
33. Shintouo CM, Mets T, Beckwee D, Bautmans I, Ghogomu SM, Souopgui J, et al. Is
inflammageing influenced by the microbiota in the aged gut? A systematic review.
Exp Gerontol. 2020;141:111079.
34. Onyango IG, Jauregui GV, Carnă M, Bennett JP Jr, Stokin GB. Neuroinflammation in
Alzheimer’s disease. Biomedicines. 2021;9(5):524.
35. Bradburn S, Sarginson J, Murgatroyd CA. Association of peripheral interleukin-6
with global cognitive decline in nondemented adults: A meta-analysis of prospective
studies. Front Aging Neurosci. 2018;9:438.
36. Marcos-Pérez D, Sánchez-Flores M, Proietti S, Bonassi S, Costa S, Teixeira JP, et al.
Association of inflammatory mediators with frailty status in older adults: Results from
a systematic review and meta-analysis. GeroScience. 2020;42(6):1451–73.
37. Picca A, Calvani R, Coelho-Júnior HJ, Marini F, Landi F, Marzetti E. Circulating
inflammatory, mitochondrial dysfunction, and senescence-related markers in older
adults with physical frailty and sarcopenia: A BIOSPHERE exploratory study. Int J
Mol Sci. 2022;23(24):14006.
38. Harré E-M, Roth J, Gerstberger R, Hübschle T. Interleukin-6 mediates
lipopolysaccharide-induced nuclear STAT3 translocation in astrocytes of rat sensory
circumventricular organs. Brain Res. 2003;980(2):151–5.
39. Jurcau A. Insights into the pathogenesis of neurodegenerative diseases: Focus on
mitochondrial dysfunction and oxidative stress. Int J Mol Sci. 2021;22(21):11847.
40. Bolaños JP, Almeida A, Moncada S. Glycolysis: A bioenergetic or a survival
pathway? Trends Biochem Sci. 2010;35(3):145–9.
41. Brand MD. The sites and topology of mitochondrial superoxide production. Exp
Gerontol. 2010;45(7–8):466–72.
42. Stefanatos R, Sanz A. The role of mitochondrial ROS in the ageing brain. FEBS Lett.
2017;592(5):743–58.

43. Jurcau A, Ardelean AI. Oxidative stress in ischemia/reperfusion injuries following
acute ischemic stroke. Biomedicines. 2022;10(3):574.
44. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species.
Mol Cell. 2012;48(2):158–67.
45. Milenkovic D, Blaza JN, Larsson NG, Hirst J. The enigma of the respiratory chain
supercomplex. Cell Metab. 2017;25(4):765–76.
46. Dikalov S. Cross talk between mitochondria and NADPH oxidases. Free Radic Biol
Med. 2011;51(7):1289–301.
47. Paß T, Wiesner RJ, Pla-Martin D. Selective neuron vulnerability in common and rare
diseases–mitochondria in the focus. Front Mol Biosci. 2021;8:676187.
48. Thomsen K, Yokota T, Hasan-Olive MM, Sherazi N, Fakouri NB, Desler C, et al.
Initial brain ageing: Heterogeneity of mitochondrial size is associated with a decline
in complex I-linked respiration in the cortex and hippocampus. Neurobiol Aging.
2018;61:215–24.
49. Stahon KE, Bastian C, Griffith S, Kidd GJ, Brunet S, Baltan S. Age-related changes
in axonal and mitochondrial ultrastructure and function in white ma tter. J
Neurosci. 2016;36(37):9990–10001.
50. Pollard AK, Craig EL, Chakrabarti L. Mitochondrial complex I activity measured by
spectrophotometry is reduced across all brain regions in ageing and more specifically
in neurodegeneration. PLoS One. 2016;11(6):e0157405.
51. Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer T, et al. Mitochondrial
DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in the
skeletal muscle of mitochondrial DNA mutator mice. PLoS One. 2010;5(7):e11468.
52. Zia A, Pourbagher-Shahri AM, Farkhondeh T, Samarghandian S. Molecular and
cellular pathways contributing to brain ageing. Behav Brain Funct. 2021;17(1):6.
53. Sharma C, Kim S, Nam Y, Jung UJ, Kim SR. Mitochondrial dysfunction as a driver of
cognitive impairment in Alzheimer’s disease. Int J Mol Sci. 2021;22(9):4850.
54. Kowald A, Kirkwood TBL. Resolving the enigma of the clonal expansion of mtDNA
deletions. Genes. 2018;9(3):126.
55. Jurcău MC, Andronie-Cioara FL, Jurcău A, Marcu F, Tit DM, Pascălău N, et al. The
link between oxidative stress, mitochondrial dysfunction and neuroinflammation in
the pathophysiology of Alzheimer’s disease: Therapeutic implications and future
perspectives. Antioxidants. 2022;11(11):2167.
56. Pinto M, Moraes CT. Mechanisms linking mtDNA damage and ageing. Free Radic
Biol Med. 2015;85:250–8.
57. Jurk D, Wang C, Miwa S, Maddick M, Korolchuk V, Tsolou A, et al. Postmitotic
neurons develop a p21-dependent senescence-like phenotype driven by a DNA
damage response. Aging Cell. 2012;11(6):996–1004.
58. Tan S, Sagara Y, Liu Y, Maher P, Schubert D. The regulation of reactive oxygen
species production during programmed cell death. J Cell Biol. 1998;141(6):1423–32.
59. Holper L, Ben-Shachar D, Mann JJ. Multivariate meta-analyses of mitochondrial
complex I and IV in major depressive disorder, bipolar disorder, schizophrenia,
Alzheimer’s disease, and Parkinson’s disease. Neuropsychopharmacology.
2019;44(5):837–49.
60. Beckervordersandforth R, Ebert B, Schäffner I, Moss J, Fiebig C, Shin J, et al. Role of
mitochondrial metabolism in the control of early lineage progression and ageing
phenotypes in adult hippocampal neurogenesis. Neuron. 2017;93(3):560–73.

Regular Issue Subscription Review Article
Volume 02
Issue 01
Received 21/01/2025
Accepted 12/02/2025
Published 17/02/2025
Publication Time 27 Days
375

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