{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:40:37Z","timestamp":1789087237762,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cognitive disorders present significant medical and social challenges nowadays, due to their high prevalence, progressive course and a lack of effective methods for treatment of neurodegenerative diseases and comorbid pathologies. An important area of research is the identification of molecular biomarkers that reflect early pathophysiological changes and facilitate a more accurate biological characterization of cognitive impairment. This study provides an overview of the most relevant signaling molecules for diagnosing cognitive disorders. It presents data on the effectiveness of using comprehensive panels of molecular biomarkers in clinical practice, including \u03b2-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, \u03b1-synuclein, and tau protein, in patients with Alzheimer\u2019s disease (AD) and vascular dementia (VD). The study results demonstrate that cumulative changes in the expression of signaling molecules reflect various neurodegenerative and vascular-associated biological processes. The data obtained are comparative in nature and require further validation before potential clinical application.<\/jats:p>","DOI":"10.3390\/ijms27010372","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Signaling Molecules and Diagnosis of Cognitive Disorders: Current State and Prospects"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-5581","authenticated-orcid":false,"given":"Igor","family":"Kvetnoy","sequence":"first","affiliation":[{"name":"Medical Institute, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia"},{"name":"Saint-Petersburg Research Institute of Phthisiopulmonology, 191036 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8276-7602","authenticated-orcid":false,"given":"Oleg","family":"Kheyfets","sequence":"additional","affiliation":[{"name":"University Hospital Wiener Neustadt, 2700 Wiener Neustadt, Austria"},{"name":"Department of Medicine, Danube Private University, 3500 Krems an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lazar","family":"Safaniev","sequence":"additional","affiliation":[{"name":"Medical Research Company \u201cA-Biomarker\u201d, 125080 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Kheifets","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Center, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-5104","authenticated-orcid":false,"given":"Ekaterina","family":"Mironova","sequence":"additional","affiliation":[{"name":"Medical Institute, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia"},{"name":"Saint-Petersburg Research Institute of Phthisiopulmonology, 191036 Saint-Petersburg, Russia"},{"name":"Saint-Petersburg Institute of Bioregulation and Gerontology, 197110 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kvetnaia","sequence":"additional","affiliation":[{"name":"Saint-Petersburg Institute of Bioregulation and Gerontology, 197110 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-7635","authenticated-orcid":false,"given":"Gianluigi","family":"Mazzoccoli","sequence":"additional","affiliation":[{"name":"Chronobiology Laboratory, Foundation IRCCS Casa Sollievo della Sofferenza, Opera di Padre Pio da Pietrelcina, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiryl","family":"Prashchayeu","sequence":"additional","affiliation":[{"name":"Medical Research Center \u00abGerontology\u00bb, 129226 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-5165","authenticated-orcid":false,"given":"Anna","family":"Gavrilova","sequence":"additional","affiliation":[{"name":"Medical Research Center \u00abGerontology\u00bb, 129226 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1468-1331.2012.03784.x","article-title":"EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia","volume":"19","author":"Sorbi","year":"2012","journal-title":"Eur. J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, X., Sun, X., Hou, N., Han, F., and Liu, Y. (2022). Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132019. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.937486"},{"key":"ref_3","unstructured":"GBD 2019 Dementia Forecasting Collaborators (2022). Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 7, e105\u2013e125."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhu, X., Yu, J., Lai, X., Wang, X., Deng, J., Yan, L., and Li, B. (2025). Global Burden of Alzheimer\u2019s disease and other dementias in adults aged 65 years and older, 1991\u20132021: Population-based study. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1585711"},{"key":"ref_5","first-page":"e70126","article-title":"Alzheimer\u2019s and dementia: Diagnosis, assessment, and disease monitoring global, regional, and national burden of Alzheimer\u2019s disease and other dementias (ADODs) and their risk factors, 1990\u20132021: A systematic analysis for the Global Burden of Disease study 2021","volume":"17","author":"Wang","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"110462","DOI":"10.1016\/j.abb.2025.110462","article-title":"Fibrillar structures detected by AFM in the cerebrospinal fluid of patients affected by Alzheimer\u2019s disease and other neurological conditions","volume":"770","author":"Polykretis","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1124\/pr.115.011833","article-title":"Endothelin","volume":"68","author":"Davenport","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_8","first-page":"731","article-title":"Clinical detenminants for the targeted effects of neurocognitive rehabilitation in elderly and senile patients with mild cognitive impairment","volume":"37","author":"Kurmyshev","year":"2024","journal-title":"Adv. Gerontol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology","volume":"81","author":"Ashton","year":"2024","journal-title":"JAMA Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.2147\/NDT.S197032","article-title":"Vascular cognitive impairment: Pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments","volume":"21","author":"Parfenov","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12987-019-0123-z","article-title":"Claudin-5: Gatekeeper of neurological function","volume":"16","author":"Greene","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer\u2019s Disease: Causes and Treatment. Molecules, 25.","DOI":"10.3390\/molecules25245789"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/procel\/pwae026","article-title":"Alzheimer\u2019s disease: Insights into pathology, molecular mechanisms, and therapy","volume":"16","author":"Zheng","year":"2025","journal-title":"Protein Cell"},{"key":"ref_16","first-page":"772","article-title":"Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13041-019-0448-1","article-title":"Blood-based molecular biomarkers for Alzheimer\u2019s disease","volume":"12","author":"Zetterberg","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-023-00403-3","article-title":"Blood biomarkers for Alzheimer\u2019s disease in clinical practice and trials","volume":"3","author":"Hansson","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jalz.2016.10.007","article-title":"The Vascular Impairment of Cognition Classification Consensus Study","volume":"13","author":"Skrobot","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3233\/JAD-221010","article-title":"Cerebrospinal Fluid sTREM-2, GFAP, and \u03b2-S100 in Symptomatic Sporadic Alzheimer\u2019s Disease: Microglial, Astrocytic, and APOE Contributions Along the Alzheimer\u2019s Disease Continuum","volume":"92","author":"Bonomi","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1161\/01.STR.0000169924.60783.d4","article-title":"Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities: Longitudinal results of the Austrian Stroke Prevention Study","volume":"36","author":"Markus","year":"2005","journal-title":"Stroke"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.conb.2021.03.003","article-title":"A current view on Tau protein phosphorylation in Alzheimer\u2019s disease","volume":"69","author":"Wegmann","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1001\/jamaneurol.2019.0765","article-title":"Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients with Alzheimer Disease","volume":"76","author":"Mattsson","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_24","first-page":"313","article-title":"Tau-protein expression in human blood lymphocytes: A promising marker and suitable sample for life-time diagnosis of Alzheimer\u2019s disease","volume":"21","author":"Kvetnoy","year":"2000","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.2147\/IJN.S200490","article-title":"Alzheimer\u2019s disease: Pathogenesis, diagnostics, and therapeutics","volume":"14","author":"Tiwari","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","article-title":"Plasma p-tau231: A new biomarker for incipient Alzheimer\u2019s disease pathology","volume":"141","author":"Ashton","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102954","DOI":"10.1016\/j.arr.2025.102954","article-title":"Next-generation biosensor technologies for Alzheimer\u2019s disease: Innovations in diagnosis, monitoring, and treatment","volume":"114","author":"Yin","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1021\/acschemneuro.4c00369","article-title":"Ultrasensitive Detection of Blood-Based Alzheimer\u2019s Disease Biomarkers: A Comprehensive SERS-Immunoassay Platform Enhanced by Machine Learning","volume":"15","author":"Resmi","year":"2024","journal-title":"ACS Chem. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pacoova Dal Maschio, V., Roveta, F., Bonino, L., Boschi, S., Rainero, I., and Rubino, E. (2025). The Role of Blood-Based Biomarkers in Transforming Alzheimer\u2019s Disease Research and Clinical Management: A Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178564"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lim, E.Y., and Kim, G.D. (2024). Particulate Matter-Induced Emerging Health Effects Associated with Oxidative Stress and Inflammation. Antioxidants, 13.","DOI":"10.3390\/antiox13101256"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3233\/JAD-200046","article-title":"Plasma Amyloid Concentration in Alzheimer\u2019s Disease: Performance of a High-Throughput Amyloid Assay in Distinguishing Alzheimer\u2019s Disease Cases from Controls","volume":"74","author":"Feinkohl","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2174\/1570159X18666201111104509","article-title":"Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer\u2019s Disease","volume":"19","author":"Hashioka","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S609","DOI":"10.3233\/JAD-2010-100564","article-title":"Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer\u2019s disease neurons","volume":"20","author":"Manczak","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1582-4934.2008.00276.x","article-title":"The ubiquitin-proteasome system in Alzheimer\u2019s disease","volume":"12","author":"Oddo","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kawahata, I., Finkelstein, D.I., and Fukunaga, K. (2022). Pathogenic Impact of \u03b1-Synuclein Phosphorylation and Its Kinases in \u03b1-Synucleinopathies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116216"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1523\/JNEUROSCI.21-09-03017.2001","article-title":"Mitochondrial abnormalities in Alzheimer\u2019s disease","volume":"21","author":"Hirai","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1161\/HYPERTENSIONAHA.119.12105","article-title":"Endothelin: 30 Years From Discovery to Therapy","volume":"74","author":"Barton","year":"2019","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.peptides.2016.05.007","article-title":"Effects of endothelin family on ANP secretion","volume":"82","author":"Yuan","year":"2016","journal-title":"Peptides"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41380-020-00923-z","article-title":"Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer\u2019s Disease Neuroimaging Initiative","volume":"26","author":"Karikari","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_40","first-page":"1471","article-title":"Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer\u2019s disease continuum","volume":"78","author":"Benedet","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1179573520907397","DOI":"10.1177\/1179573520907397","article-title":"Current and future treatments in alzheimer disease: An update","volume":"12","author":"Yiannopoulou","year":"2020","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_42","first-page":"23","article-title":"Brain perfusion, cognitive function and vascular age in middle-aged patients with essential arterial hypertension","volume":"58","author":"Parfenov","year":"2018","journal-title":"Cardiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"118677","DOI":"10.1016\/j.bbamcr.2020.118677","article-title":"Role of S100 proteins in health and disease","volume":"1867","author":"Gonzalez","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41591-020-0762-2","article-title":"Diagnostic value of plasma phosphorylated tau181 in Alzheimer\u2019s disease and frontotemporal lobar degeneration","volume":"26","author":"Thijssen","year":"2020","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3233\/JAD-200861","article-title":"A Sensitive and Cost-Effective Chemiluminescence ELISA for Measurement of Amyloid-\u03b2 1\u201342 Peptide in Human Plasma","volume":"78","author":"Mehta","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.3233\/JAD-170950","article-title":"Low Cerebrospinal Fluid A\u03b242 and A\u03b240 are Related to White Matter Lesions in Cognitively Normal Elderly","volume":"62","author":"Skoog","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Arcaro, M., Fenoglio, C., Serpente, M., Arighi, A., Fumagalli, G.G., Sacchi, L., Floro, S., D\u2019Anca, M., Sorrentino, F., and Visconte, C. (2022). A Novel Automated Chemiluminescence Method for Detecting Cerebrospinal Fluid Amyloid-Beta 1\u201342 and 1\u201340, Total Tau and Phosphorylated-Tau: Implications for Improving Diagnostic Performance in Alzheimer\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102667"},{"key":"ref_49","first-page":"e12008","article-title":"Plasma Lipids as Biomarkers for Alzheimer\u2019s Disease: A Systematic Review","volume":"12","author":"Agarwal","year":"2020","journal-title":"Cureus"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yang, W., Guan, F., Yang, L., Shou, G., Zhu, F., Xu, Y., Meng, Y., Li, M., and Dong, W. (2024). Highly sensitive blood-based biomarkers detection of beta-amyloid and phosphorylated-tau181 for Alzheimer\u2019s disease. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1445479"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s44328-025-00040-3","article-title":"Optical biosensors for diagnosing neurodegenerative diseases","volume":"2","author":"Su","year":"2025","journal-title":"NPJ Biosens."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"128009","DOI":"10.1016\/j.talanta.2025.128009","article-title":"Competitive electrochemical immunosensor for trace phosphorylated Tau181 analysis in plasma: Toward point-of-care technologies of Alzheimer\u2019s disease","volume":"292","author":"Luo","year":"2025","journal-title":"Talanta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:32:37Z","timestamp":1767195157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010372"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010372","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,29]]}}}