THE ROLE OF BETA-AMYLOID IN NORM AND AT ALZHEIMER`S DISEASE
Yu. N. Tyshchenko, E.A. Lukyanetz
O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz66.06.088

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and memory
loss. The pathogenesis of AD is complex, depends on many
factors, and has not yet been fully studied. Extracellular deposits of amyloid-β (Aβ) peptide in the form of senile plaques, the
formation of intracellular neurofibrillary tangles, and massive
neuronal loss are considered as the main pathological signs
of AD. However, recently there have been many data that
indicate other pathways involved in the pathogenesis of AD.
This review aims to analyze the existing data on the physiological role of Aβ in the brain under normal conditions and
its pathological role in Alzheimer’s disease.
Keywords:
amyloid-β; Alzheimer’s disease; cognitive functions; neurodegeneration.
References
- Alzheimer Association. 2020 Alzheimer's disease facts and figures. Alzheimer's Dement. 2020.
- Alzheimer's disease international. World Alzheimer Report 2019. Prim Care Ment Heal Older People. 2019;311-29.
- C. Crdenas-Aguayo M del, C. Silva-Lucero M del, CortesOrtiz M, Jimnez-Ramos B, Gmez-Virgilio L, RamrezRodrguez G, et al. Physiological role of amyloid beta in neural cells: The cellular trophic activity. In: Heinbockel T, ed. Neurochemistry. IntechOpen. 2014. 4. Luna S, Cameron DJ, Ethell DW. Amyloid-β and APP deficiencies cause severe cerebrovascular defects: important work for an old villain. PLoS One. 2013 Sep 5;8(9).
CrossRef
PubMed PubMedCentral
- Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. Alzheimer's disease-associated amyloid β-protein is an antimicrobial peptide. PLoS One. 2010 Mar 3;5(3):1-10.
CrossRef
PubMed PubMedCentral
- Bhadbhade A, Cheng DW. Amyloid precursor protein processing in Alzheimer's disease. Iran J Child Neurol. 2012;6(1):1-4.
- Wälti MA, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, et al. Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril. Proc Natl Acad Sci USA. 2016 Aug 23;113(34):E4976-84.
CrossRef
PubMed PubMedCentral
- Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptordependent signaling pathway. J Neurosci. 2007 Mar 14;27(11):2866-75.
CrossRef
PubMed PubMedCentral
- Puzzo D, Privitera L, Leznik E, Fà M, Staniszewski A, Palmeri A, Arancio O. Picomolar amyloid-β positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008;28(53):14537-45.
CrossRef
PubMed PubMedCentral
- Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA. The production of amyloid β peptide is a critical requirement for the viability of central neurons. J Neurosci. 2003;23(13):5531-5.
CrossRef
PubMed PubMedCentral
- Cirrito JR, May PC, O'Dell MA, Taylor JW, Parsadanian M, Cramer JW, Audia JE, Nissen JS, Bales KR, Paul SM, DeMattos RB, Holtzman DM. In vivo assessment of brain interstitial fluid with microdialysis reveals plaqueassociated changes in amyloid-β metabolism and half-life. J Neurosci. 2003;23(26):8844-53.
CrossRef
PubMed PubMedCentral
- Pearson HA, Peers C. Physiological roles for amyloid β peptides. J Physiol. 2006 Aug;575(Part 1):5-10.
CrossRef
PubMed PubMedCentral
- Cuello AC. Intracellular and extracellular Aβ, a tale of two neuropathologies. Brain Pathol. 2006;15(1):66-71.
CrossRef
PubMed
- Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ. The oligomerization of amyloid β-protein begins intracellularly in cells derived from human brain. Biochemistry. 2000;39(35):10831-9.
CrossRef
PubMed
- Lane CA, Hardy J, Schott JM. Alzheimer's disease. Eur J Neurol. 2018;25(1):59-70.
CrossRef
PubMed
- Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, et al. Identification of the major Aβ1- 42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nat Med. 2000;6(2):143-50.
CrossRef
PubMed
- Glabe CC. Amyloid accumulation and pathogensis of Alzheimer's disease: significance of monomeric, oligomeric and fibrillar Abeta. Subcell Biochem. 2005;38:167-77.
CrossRef
PubMed
- Walsh DM, Klyubin I, Fadeeva J V., Rowan MJ, Selkoe DJ. Amyloid-β oligomers: Their production, toxicity and therapeutic inhibition. Biochem Soc Trans. 2002;30(4):552-7.
CrossRef
PubMed
- Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999;399(June):A23-31.
CrossRef
PubMed
- Mikheytseva I.N. Molecular mechanisms of neurodegeneration in primary glaucoma pathogenesis, retinoneuroprotective action of melatonin. Tavricheskiy Med Vestn. 2012;231-4.
- Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-95.
CrossRef
PubMed
- Madeo F, Tavernarakis N, Kroemer G. Can autophagy promote longevity? Nat Cell Biol. 2010;12(9):842-6.
CrossRef
PubMed
- Park D, Jeong H, Lee MN, Koh A, Kwon O, Yang YR, Noh J, Suh PG, Park H, Ryu SH. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition. Sci Rep. 2016;6:21772.
CrossRef
PubMed PubMedCentral
- Meiliana A, Dewi NM, Wijaya A. New insight in the molecular mechanisms of neurodegenerative disease. Indones Biomed J. 2018;10(1):16-34.
CrossRef
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The Hallmarks of aging longevity. Cell. 2013;153(6):1194-217.
CrossRef
PubMed PubMedCentral
- Scheibye-knudsen M, Fang EF, Croteau DL, Bohr VA. Protecting the mitochondrial powerhouse. trends Cell Biol., 2015;25(3):158-70.
CrossRef
PubMed PubMedCentral
- Kravenska Y, Nieznanska H, Nieznanski K, Lukyanetz E, Szewczyk A, Koprowski P. The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism. Biochim Biophys Acta - Biomembr. 2020;1862(9):183337.
CrossRef
PubMed
- Kravenska EV, Chopovska VV Yavorskaya EN, Lukyanetz EA. The role of mitochondria in the developmenr of Alzheimer's disease. Tavricheskiy Med Biol Bull. 2012;15 (3/2):147-9.
- Tu Y, Chen C, Pan J, Xu J, Zhou ZG, Wang CY. The ubiquitin proteasome pathway (UPP) in the regulation of cell cycle control and DNA damage repair and its implication in tumorigenesis. Int J Clin Exp Pathol. 2012;5(8):726-38.
- Song S, Kim SY, Hong YM, Jo DG, Lee JY, Shim SM, Chung CW, Seo SJ, Yoo YJ, Koh JY, Lee MC, Yates AJ, Ichijo H, Jung YK. Essential role of E2-25K/ Hip-2 in mediating amyloid-β neurotoxicity. Mol Cell. 2003;12(3):553-63.
CrossRef
PubMed
- Aaron Ciechanover and PB. The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg Review. Neuron. 2003;40(2):427-46.
CrossRef
- Bertrand P. Tseng, Kim N. Green, Julie L. Chan, Mathew Blurton-Jones and FML. Aβ inhibits the proteasome and enhances amyloid and tauaccumulation. Neurobiol Aging. 2008;29(11):1607-18.
CrossRef
PubMed PubMedCentral
- Gadhave K, Bolshette N, Ahire A, Pardeshi R, Thakur K, Trandafir C, Istrate A, Ahmed S, Lahkar M, Muresanu DF, Balea M. The ubiquitin proteasomal system: a potential target for the management of Alzheimer's disease. J Cell Mol Med. 2016;20(7):1392-407.
CrossRef
PubMed PubMedCentral
- Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid β-peptide. Nat Rev Mol Cell Biol. 2007;8(2):101-12.
CrossRef
PubMed
- Sipos E, Kurunczi A, Kasza Á, Horváth J, Felszeghy K, Laroche S, Toldi J, Párducz Á, Penke B, Penke Z. β-Amyloid pathology in the entorhinal cortex of rats induces memory deficits: Implications for Alzheimer's disease. Neuroscience. 2007;147(1):28-36.
CrossRef
PubMed
- Maurice T, Lockhart BP, Privat A. Amnesia induced in mice by centrally administered β-amyloid peptides involves cholinergic dysfunction. Brain Res. 1996;706(2):181-93.
CrossRef
Gaugler J, James B, Johnson T, Scholz K, Weuve J. 2016 Alzheimer's disease facts and figures. Alzheimer's Dement [Internet]. 2016;12(4):459-509. Available from: http:// dx.doi.org/10.1016/j.jalz.2016.03.001
CrossRef
PubMed
- Garcia-Osta A, Alberini CM. Amyloid beta mediates memory formation. Learn Mem. 2009;16(4):267-72.
CrossRef
PubMed PubMedCentral
Morley J, Farr S, Banks W, Johnson S, Yamada K, Xu L. A physiological role for amyloid beta protein: Enhancement of learning and memory. Nat Preced [Internet]. 2008 Jul 25 [cited 2020 Feb 24]; Available from: http://www.nature. com/articles/npre.2008.2119.1
- Morley JE, Farr SA, Nguyen AD, Xu F. What is the Physiological Function of Amyloid-Beta Protein? J Nutr Heal Aging. 2019 Mar 1;23(3):225-6.
CrossRef
PubMed
- Morley JE, Farr SA. Hormesis and amyloid-β protein: Physiology or pathology? J Alzheimer's Dis. 2012;29(3):487-92.
CrossRef
PubMed
Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol [Internet]. 2014;88(4):479-85. Available from: http://dx.doi. org/10.1016/j.bcp.2013.12.018
CrossRef
PubMed
- Peter T. Nelson, MD, PhD, Irina Alafuzoff, MD, PhD, Eileen H. Bigio, MD, Constantin Bouras, MD, Heiko Braak, MD, Nigel J. Cairns, PhD, FRCPath, Rudolph J. Castellani, MD, Barbara J. Crain, MD, PhD, Peter Davies, PhD, Kelly Del Tredici, MD, PhD, Charles Du P. Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature. J Neuropathol Exp Neurol. 2012;71(5):362-81.
CrossRef
PubMed PubMedCentral
- Tyshchenko YM, Lukyanetz EA. Effects of memantine on behavioral indices of rats in the open field. Neurophysiology. 2017;49(6):453-7.
CrossRef
- Kruchenko ZA, Gorbachenko VA, Chereda IS, Lukyanetz EA. Effect of memantine on motor behavioral phenomena in rats of different ages. Neurophysiology. 2014;46(5):448-51.
CrossRef
- Bergmann K, Tomlinson BE, Blessed G, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978;2(6150):1457-9.
CrossRef
PubMed PubMedCentral
- Fleisher AS, Sowell BB, Taylor C, Gamst AC, Petersen RC, Thal LJ. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2007;68(19):1588-95.
CrossRef
PubMed
- Van Dyck CH, Tariot PN, Meyers B, Malca Resnick E. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21(2):136-43.
CrossRef
PubMed
- Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer's disease. Hum Mol Genet. 2010 Apr 22;19(R1):12-20.
CrossRef
PubMed PubMedCentral
- Rockenstein E, Adame A, Mante M, Moessler H, Windisch M, Masliah E. The neuroprotective effects of CerebrolysinTM in a transgenic model of Alzheimer's disease are associated with improved behavioral performance. J Neural Transm. 2003;110(11):1313-27.
CrossRef
PubMed
- Ringman J, Frautschy S, Cole G, Masterman D, Cummings J. A potential role of the curry spice curcumin in Alzheimers disease. Curr Alzheimer Res. 2005;2(2):131-6.
CrossRef
PubMed PubMedCentral
- Lipton S. The molecular basis of memantine action in Alzheimers disease and other neurologic disorders: Lowaffinity, uncompetitive antagonism. Curr Alzheimer Res. 2005;2(2):155-65.
CrossRef
PubMed
- Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model. Science (80- ). 2007 May 4;316(5825):750-4.
CrossRef
PubMed
- Andorfer C, Kress Y, Espinoza M, De Silva R, Tucker KL, Barde YA, Duff K, Davies P. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J Neurochem. 2003;86(3):582-90.
CrossRef
PubMed
- Wuli W, Tsai ST, Chiou TW, Harn HJ. Human-induced pluripotent stem cells and herbal small-molecule drugs for treatment of Alzheimer's disease. Int J Mol Sci. 2020;21(4).
CrossRef
PubMed PubMedCentral
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