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Abstract

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

by
Yulia K. Styufliaeva
1,2,*,
Andrew A. Zelinsky
2,
Oksana A. Malikova
2 and
Aleksandr A. Rubel
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
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 Contributions

Conceptualization, 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.

Funding

This research was supported by St. Petersburg State University (project No. 95444727).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors acknowledge Yury O. Chernoff, for valuable comments and Core Facility “Chromas” (Research Park, St. Petersburg State University) for technical assistance.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Kulichikhin, 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]
  2. 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]
  3. 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]
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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

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