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Proteomic Markers and Early Prediction of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common socially significant neurodegenerative pathology, which currently affects more than 30 million elderly people worldwide. Since the number of patients grows every year and may exceed 115 million by 2050, and due to the lack of effective therapies, early prediction of AD remains a global challenge, solution of which can contribute to the timely appointment of a preventive therapy in order to avoid irreversible changes in the brain. To date, clinical assays for the markers of amyloidosis in cerebrospinal fluid (CSF) have been developed, which, in conjunction with the brain MRI and PET studies, are used either to confirm the diagnosis based on obligate clinical criteria or to predict the risk of AD developing at the stage of mild cognitive impairment (MCI). However, the problem of predicting AD at the asymptomatic stage remains unresolved. In this regard, the search for new protein markers and studies of proteomic changes in CSF and blood plasma are of particular interest and may consequentially identify particular pathways involved in the pathogenesis of AD. Studies of specific proteomic changes in blood plasma deserve special attention and are of increasing interest due to the much less invasive method of sample collection as compared to CSF, which is important when choosing the object for large-scale screening. This review briefly summarizes the current knowledge on proteomic markers of AD and considers the prospects of developing reliable methods for early identification of AD risk factors based on the proteomic profile.

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Abbreviations

Aβ:

amyloid-β peptides

ACE:

angiotensin converting enzyme

AD:

Alzheimer’s disease

APP:

amyloid precursor protein

Apo:

apolipoprotein

BACE1:

beta-secretase 1

CB:

candidate biomarker

CSF:

cerebrospinal fluid

IL:

interleukin

MCI:

mild cognitive impairment

MS:

mass spectrometry

NfL:

neurofilament light chain

sTREM2:

soluble form of triggering receptor expressed on myeloid cells 2

t-tau and p-tau:

total and phosphorylated tau proteins, respectively

TNF:

tumor necrosis factor

VILIP-1:

visin-like-protein-1

YKL-40:

chitinase-3 like-1

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Funding

This work was financially supported by the Megagrant of Ministry of Science and Higher Education of the Russian Federation [Agreement with Skolkovo Institute of Science and Technology, no. 075-10-2022-090 (075-10-2019-083)].

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Authors and Affiliations

  1. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, 119334, Moscow, Russia

    Natalia V. Zakharova, Anna E. Bugrova & Maria I. Indeykina

  2. Mental Health Research Center, 115522, Moscow, Russia

    Yana B. Fedorova, Igor V. Kolykhalov & Svetlana I. Gavrilova

  3. Skolkovo Institute of Science and Technology, 121205, Moscow, Russia

    Evgeny N. Nikolaev & Alexey S. Kononikhin

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  1. Natalia V. Zakharova
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Contributions

Conceptualization, N.V.Z., A.S.K., S.I.G., and E.N.N.; analysis of publications, selection of material, N.V.Z., A.E.B., M.I.I., Y.B.F., and I.V.K.; data analysis and preparation of table and figures, N.V.Z., A.E.B., M.I.I., and A.S.K.; writing – original draft preparation, N.V.Z., A.E.B., M.I.I., and Y.B.F.; writing – review and editing, A.S.K., I.V.K., S.I.G., and E.N.N. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Natalia V. Zakharova or Alexey S. Kononikhin.

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The authors declare no conflicts of interest in financial or any other sphere. This article does not include the experiments involving humans or animals performed by any of the authors.

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Zakharova, N.V., Bugrova, A.E., Indeykina, M.I. et al. Proteomic Markers and Early Prediction of Alzheimer’s Disease. Biochemistry Moscow 87, 762–776 (2022). https://doi.org/10.1134/S0006297922080089

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