The Development of an Early Diagnostic Method for Alzheimer’s Disease

first_page Download PDF settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessAbstract The Development of an Early Diagnostic Method for Alzheimer's Disease † by Yulia K. StyufliaevaYulia K. Styufliaeva SciProfiles Scilit Preprints.org Google Scholar 1,2,*, Andrew A. ZelinskyAndrew A. Zelinsky SciProfiles Scilit Preprints.org Google Scholar 2, Oksana A. MalikovaOksana A. Malikova SciProfiles Scilit Preprints.org Google Scholar 2 and Aleksandr A. RubelAleksandr A. Rubel SciProfiles Scilit Preprints.org Google Scholar 2 1 SCAMT Institute, ITMO University, 197101 St. Petersburg, Russia 2 Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia * Author to whom correspondence should be addressed. † Presented at the 3rd International Electronic Conference on Biomolecules, 23–25 April 2024; Available online: https://sciforum.net/event/IECBM2024. Proceedings 2024, 103(1), 83; https://doi.org/10.3390/proceedings2024103083 Published: 12 April 2024 (This article belongs to the Proceedings of The 3rd International Electronic Conference on Biomolecules) Download keyboard_arrow_down Download PDF Download PDF with Cover Download XML Download Epub Versions Notes Keywords: Alzheimer's Disease (AD); aggregates; amyloid beta (Aβ); Protein Misfolding Cyclic Amplification (PMCA); neuronal degeneration Alzheimer's disease (AD) is the most common form of dementia, characterized by neuronal degeneration and death. The appearance of aggregated forms of the Aβ42 peptide is a key biochemical marker indicating the possible initiation of the pathological cascade in Alzheimer's disease [1].The goal of this study is to develop an approach for the early diagnosis of AD by detecting Aβ42 multimers in the blood and lymph.We adapted the Protein Misfolding Cyclic Amplification (PMCA) method [2] for the detection of Aβ42 aggregates in blood samples. One of the main challenges in using the PMCA method for detecting Aβ42 aggregates is that the synthesized or recombinant Aβ42 peptide spontaneously aggregates with high yield. Therefore, it is difficult to distinguish spontaneous aggregation from aggregation induced by externally added aggregated Aβ42, e.g., from the patient's samples.Previously, using a yeast model [3], we identified mutations in human Aβ42 that reduce its aggregation propensity. In this study, we isolated and purified the wild-type Aβ42 and five recombinant Aβ42 variants with mutations that decrease Aβ42 aggregation via metal-affinity chromatography. We investigated the aggregation kinetics of these Aβ42 variants in the presence of thioflavin T using fluorometry. Currently, we are studying the aggregation kinetics of different Aβ42 variants in the presence of aggregated wild-type Aβ42.We believe that our findings will help develop an effective system for detecting multimeric forms of the Aβ peptide in the blood at extremely low levels to be used as a biomarker for diagnosing AD before the onset of any clinical symptoms. Author ContributionsConceptualization, A.A.R.; data acquisition and formal analysis, Y.K.S., A.A.Z. and O.A.M.; supervision, A.A.R.; funding acquisition, A.A.R.; writing—review and editing, Y.K.S. and A.A.R. All authors have read and agreed to the published version of the manuscript.FundingThis research was supported by St. Petersburg State University (project No. 95444727).Institutional Review Board StatementNot applicable.Informed Consent StatementNot applicable.Data Availability StatementNot applicable.AcknowledgmentsThe authors acknowledge Yury O. Chernoff, for valuable comments and Core Facility "Chromas" (Research Park, St. Petersburg State University) for technical assistance.Conflicts of InterestThe authors declare no conflict of interest.ReferencesKulichikhin, K.Y.; Malikova, O.A.; Zobnina, A.E.; Zalutskaya, N.M.; Rubel, A.A. Interaction of Proteins Involved in Neuronal Proteinopathies. Life 2023, 13, 1954. [Google Scholar] [CrossRef] [PubMed]Castilla, J.; Saá, P.; Morales, R.; Abid, K.; Maundrel, K.; Soto, C. Protein misfolding cyclic amplification for diagnosis and prion propagation studies. Methods Enzymol. 2006, 412, 3–21. [Google Scholar] [CrossRef] [PubMed]Chandramowlishwaran, P.; Sun, M.; Casey, K.L.; Romanyuk, A.V.; Grizel, A.V.; Sopova, J.V.; Rubel, A.A.; Nussbaum-Krammer, C.; Vorberg, I.M.; Chernoff, Y.O. Mammalian amyloidogenic proteins promote prion nucleation in yeast. J. Biol. Chem. 2018, 293, 3436–3450. [Google Scholar] [CrossRef] [PubMed]Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Share and Cite MDPI and ACS Style Styufliaeva, Y.K.; Zelinsky, A.A.; Malikova, O.A.; Rubel, A.A. The Development of an Early Diagnostic Method for Alzheimer's Disease. Proceedings 2024, 103, 83. https://doi.org/10.3390/proceedings2024103083 AMA Style Styufliaeva YK, Zelinsky AA, Malikova OA, Rubel AA. The Development of an Early Diagnostic Method for Alzheimer's Disease. Proceedings. 2024; 103(1):83. https://doi.org/10.3390/proceedings2024103083 Chicago/Turabian Style Styufliaeva, Yulia K., Andrew A. Zelinsky, Oksana A. Malikova, and Aleksandr A. Rubel. 2024. "The Development of an Early Diagnostic Method for Alzheimer's Disease" Proceedings 103, no. 1: 83. https://doi.org/10.3390/proceedings2024103083 Article Metrics No No Article Access Statistics Multiple requests from the same IP address are counted as one view.