About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
ISSN 0300-9092 (Print)
ISSN 2412-5679 (Online)
About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
Logout
Obstetrics and Gynegology2026№6

The role of tau protein in the etiopathogenesis of preeclampsia as a proteinopathy in the second half of pregnancy

DOI
https://dx.doi.org/10.18565/aig.2026.25

Sidorova I.S., Murashko A.V., Managadze I.D.

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia

Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality; however, its etiopathogenesis remains unclear, highlighting the need for new conceptual approaches to the study of this complication. In this article preeclampsia is considered as a systemic proteinopathy of the second half of pregnancy, a consequence of a neurogenic, neuroimmune, complement-mediated conflict between the mother and the fetus, associated with the production of barrier-crossing neuron-specific proteins in the fetal brain during the critical period of neurocorticogenesis after 22–24 weeks of gestation.
The aim of this review is to highlight the role of tau protein, particularly its pathological, toxic cis conformation (cis P-tau), in the cascade of pathophysiological changes in preeclampsia, taking into account the structural and functional characteristics of tau protein and the mechanisms of its pathological transformation, systemic spread leading to the formation of cistauosis, impairment of the autophagy process, and the use of tau protein as a target for diagnostic and therapeutic interventions.
Conclusion. The concept presented here describes preeclampsia as a unique multisystem ‘tautopathy’ of perinatal period, based on a neuroimmune conflict mediated by the neuron-specific proteins of the fetal brain, with a key role played by tau protein, which determines the severity and organ-specificity of preeclampsia clinical picture. This explains the temporal progression of preeclampsia and the diversity of its manifestations, and opens up entirely new directions for the development of pathogenetically based methods of diagnosis and treatment.

Authors’ contributions. Sidorova I.S., Murashko A.V., Managadze I.D. – developing the concept and design of the study, editing the text, collection and analysis of literary data, writing the text.
Conflicts of interest. Authors declare lack of the possible conflicts of interests.
Funding. The study was conducted without sponsorship.
Generative Artificial Intelligence. The authors did not use artificial intelligence tools to create the text of the article.
For citation: Sidorova I.S., Murashko A.V., Managadze I.D. The role of tau protein in the 
etiopathogenesis of preeclampsia as a proteinopathy in the second half of pregnancy.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (6): 5-13 (in Russian)
https://dx.doi.org/10.18565/aig.2026.25

Keywords

preeclampsia
neuron-specific proteins
tau protein
cis P-tau
hyperphosphorylation
Pin-1
autophagy
BBB
targeted therapy for preeclampsia
Full text (in Russian)

References

  1. Борис Д.А., Шмаков Р.Г. Преэклампсия: современные концепции патогенеза. Акушерство и гинекология. 2022; 12: 12-7. https://dx.doi.org/10.18565/aig.2022.213 [Boris D.A., Shmakov R.G. Preeclampsia: modern concepts of pathogenesis. Obstetrics and Gynecology. 2022; (12): 12-7 (in Russian). https://dx.doi.org/10.18565/aig.2022.213].
  2. Gestational hypertension and preeclampsia. ACOG Practice Bulletin, Number 222. Obstet. Gynecol. 2020; 135(6): e237-e260. https://dx.doi.org/10.1097/AOG.0000000000003891
  3. Федеральная служба государственной статистики (Росстат). Здравоохранение в России 2025. Статистический сборник. М.: Росстат; 2025. 149 с. [Federal State Statistics Service (Rosstat). Healthcare in Russia 2025. Statistical collection. Moscow: Rosstat; 2025. 149 p. (in Russian)].
  4. Medegan Fagla B., Buhimschi I.A. Protein misfolding in pregnancy: current insights, potential mechanisms, and implications for the pathogenesis of preeclampsia. Molecules. 2024; 29(3): 610. https://dx.doi.org/10.3390/molecules29030610
  5. Amabebe E., Huang Z., Jash S., Krishnan B., Cheng S., Nakashima A. et al. Novel role of Pin1-Cis P-Tau-ApoE axis in the pathogenesis of preeclampsia and its connection with dementia. Biomedicines. 2024; 13(1): 29. https://dx.doi.org/10.3390/biomedicines13010029
  6. Fiock K.L., Smalley M.E., Crary J.F., Pasca A.M., Hefti M.M. Increased tau expression correlates with neuronal maturation in the developing human cerebral cortex. eNeuro. 2020; 7(3): ENEURO.0058-20.2020. https://dx.doi.org/10.1523/ENEURO.0058-20.2020
  7. Canepa E., Fossati S. Impact of tau on neurovascular pathology in Alzheimer's disease. Front. Neurol. 2021; 11: 573324. https://dx.doi.org/10.3389/fneur.2020.573324
  8. Jash S., Banerjee S., Cheng S., Wang B., Qiu C., Kondo A. et al. Cis P-Tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia. Nat. Commun. 2023; 14(1): 5414. https://dx.doi.org/10.1038/s41467-023-41144-6
  9. Qiu C., Li Z., Leigh D.A., Duan B., Stucky J.E., Kim N. et al. The role of the Pin1-cis P-tau axis in the development and treatment of vascular contribution to cognitive impairment and dementia and preeclampsia. Front. Cell Dev. Biol. 2024; 12: 1343962. https://dx.doi.org/10.3389/fcell.2024.1343962
  10. Michalicova A., Majerova P., Kovac A. Tau protein and its role in blood-brain barrier dysfunction. Front. Mol. Neurosci. 2020; 13: 570045. https://dx.doi.org/10.3389/fnmol.2020.570045
  11. Shen X., Li H., Zhang B., Li Y., Zhu Z. Tau-targeted therapeutic strategies: mechanistic targets, clinical pipelines, and analysis of failures. Cells. 2025; 14(19): 1506. https://dx.doi.org/10.3390/cells14191506
  12. Combs B., Mueller R.L., Morfini G., Brady S.T., Kanaan N.M. Tau and axonal transport misregulation in tauopathies. Adv. Exp. Med. Biol. 2019; 1184: 81-95. https://dx.doi.org/10.1007/978-981-32-9358-8_7
  13. Chinnathambi S., Rangappa N. SUMO inhibits Tau aggregation in Alzheimer's disease. Adv. Protein Chem. Struct. Biol. 2025; 147: 355-74. https://dx.doi.org/10.1016/bs.apcsb.2025.02.001
  14. Wang R., Lu K.P., Zhou X.Z. Function and regulation of cis P-tau in the pathogenesis and treatment of conventional and nonconventional tauopathies. J. Neurochem. 2023; 166: 904-14. https://dx.doi.org/10.1111/jnc.15909
  15. Wang L., Zhou Y., Chen D., Lee T.H. Peptidyl-prolyl cis/trans isomerase Pin1 and Alzheimer's disease. Front. Cell Dev. Biol. 2020; 8: 355. https://dx.doi.org/10.3389/fcell.2020.00355
  16. Jeong J., Usman M., Li Y., Zhou X.Z., Lu K.P. Pin1-catalyzed conformation changes regulate protein ubiquitination and degradation. Cells. 2024; 13(9): 731. https://dx.doi.org/10.3390/cells13090731
  17. Xia Y., Prokop S., Giasson B.I. “Don’t Phos Over Tau”: Recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol. Neurodegener. 2021; 16: 37. https://dx.doi.org/10.1186/s13024-021-00460-5
  18. Cline E.N., Bicca M.A., Viola K.L., Klein W.L. The amyloid-β oligomer hypothesis: beginning of the third decade. Journal of Alzheimer’s Disease. 2018; 64(s1): S567-S610. https://dx.doi.org/10.3233/JAD-179941
  19. Koike H., Iguchi Y., Sahashi K., Katsuno M. Significance of oligomeric and fibrillar species in amyloidosis: insights into pathophysiology and treatment. Molecules. 2021; 26(16): 5091. https://dx.doi.org/10.3390/molecules26165091
  20. Plácido A.I., Pereira C.M.F., Correira S.C., Carvalho C., Oliveira C.R., Moreira P.I. Phosphatase 2A inhibition affects endoplasmic reticulum and mitochondria homeostasis via cytoskeletal alterations in brain endothelial cells. Mol. Neurobiol. 2017; 54(1): 154-68. https://dx.doi.org/10.1007/s12035-015-9640-1
  21. Niewiadomska G., Niewiadomski W., Steczkowska M., Gasiorowska A. Tau oligomers neurotoxicity. Life (Basel). 2021; 11(1): 28. https://dx.doi.org/10.3390/life11010028
  22. Chiti F., Dobson C.M. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu. Rev. Biochem. 2017; 86(1): 27-68. https://dx.doi.org/10.1146/annurev-biochem-061516-045115
  23. Guo T., Noble W., Hanger D.P. Roles of tau protein in health and disease. Acta. Neuropathol. 2017; 133(5): 665-704. https://dx.doi.org/10.1007/s00401-017-1707-9
  24. Lu K.P., Zhou X.Z. Pin1-catalyzed conformational regulation after phosphorylation: a distinct checkpoint in cell signaling and drug discovery. Sci. Signal. 2024; 17(841) eadi8743. https://dx.doi.org/10.1126/scisignal.adi8743
  25. Lederer W., Dominguez C.A., Popovscaia M., Putz G., Humpel C. Cerebrospinal fluid levels of tau and phospho-tau-181 proteins during pregnancy. Pregnancy Hypertens. 2016; 6(4): 384-7. https://dx.doi.org/10.1016/j.preghy.2016.08.243
  26. Bergman L., Zetterberg H., Kaihola H., Hagberg H., Blennow K., Åkerud H. Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study. PLoS One. 2018; 13(5): e0196025. https://dx.doi.org/10.1371/journal.pone.0196025
  27. Sharma S. Autophagy-based diagnosis of pregnancy hypertension and pre-eclampsia. Am. J. Pathol. 2018; 188(11): 2457-60. https://dx.doi.org/110.1016/j.ajpath.2018.09.001
  28. Aoki A., Nakashima A., Kusabiraki T., Ono Y., Yoshino O., Muto M. et al. Trophoblast-specific conditional Atg7 knockout mice develop gestational hypertension. Am. J. Pathol. 2018; 188(11): 2474-86. https://dx.doi.org/10.1016/j.ajpath.2018.07.021
  29. Qiu C., Albayram O., Kondo A., Wang B., Kim N., Arai K. et al. Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice. Sci. Transl. Med. 2021; 13(596): eaaz7615. https://dx.doi.org/10.1126/scitranslmed.aaz7615
  30. Huebner H., Knoerr B., Betzler A., Hartner A., Kehl S., Baier F. et al. Detyrosinatedtubulin is decreased in fetal vessels of preeclampsia placentas. Placenta. 2018; 62: 58-65. https://dx.doi.org/10.1016/j.placenta.2017.12.019
  31. Wu Y.C., Bogale T.A., Koistinaho J., Pizzi M., Rolova T., Bellucci A. The contribution of β-amyloid, Tau and α-synuclein to blood-brain barrier damage in neurodegenerative disorders. Acta Neuropathol. 2024; 147(1): 39. https://dx.doi.org/10.1007/s00401-024-02696-z
  32. Majerova P., Michalicova A., Cente M., Hanes J., Vegh J., Kittel A. et al. Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies. PLoS One. 2019; 14(5): e0217216. https://dx.doi.org/10.1371/journal.pone.0217216
  33. Escudero C., Kupka E., Ibañez B., Sandoval H., Troncoso F., Wikström A.K. et al. Brain vascular dysfunction in mothers and their children exposed to preeclampsia. Hypertension. 2022; 79: 242-56. https://dx.doi.org/10.1161/HYPERTENSIONAHA.122.19408
  34. Bergman L., Hastie R., Bokstrom-Rees E., Zetterberg H., Blennow K., Schell S. et al. Cerebral biomarkers in neurologic complications of preeclampsia. Am. J. Obstet. Gynecol. 2022; 227(2): 298e1-10. https://dx.doi.org/10.1016/j.ajog.2022.02.036
  35. Kaur S., Darden C.J., Adegbola G.M., Warrington J.P. History of hypertensive disorders of pregnancy and risk of Alzheimer's disease and vascular dementia. Front. Neuroendocrinol. 2025; 78: 101198. https://dx.doi.org/10.1016/j.yfrne.2025.101198
  36. Huang Z., Cheng S., Jash S., Fierce J., Agudelo A., Higashiyama T. et al. Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy. Exp. Mol. Med. 2024; 56(5): 1206-20. https://dx.doi.org/10.1038/s12276-024-01234-x
  37. Сидорова И.С., Никитина Н.А. Обоснование современной концепции развития преэклампсии. Акушерство и гинекология. 2019; 4: 26-33. https://dx.doi.org/10.18565/aig.2019.4.26-33 [Sidorova I.S., Nikitina N.A. Validation of the modern concept of the development of preeclampsia. Obstetrics and Gynecology. 2019; (4): 26-33 (in Russian). https://dx.doi.org/10.18565/aig.2019.4.26-33].
  38. Zhou P., Wang J., Wang J., Liu X. When autophagy meets placenta development and pregnancy complications. Front. Cell Dev. Biol. 2024; 12: 1327167. https://dx.doi.org/10.3389/fcell.2024.1327167
  39. Ribeiro V.R., Romao-Veiga M., Nunes P.R., Peracoli J.C., Peracoli M.T.S. Increase of autophagy marker p62 in the placenta from pregnant women with preeclampsia. Hum. Immunol. 2022; 83(10022): 447-52. https://dx.doi.org/10.1016/j.humimm.2022.02.005
  40. Zheng W., Zhang Y., Xu P., Wang Z., Shao X., Chen C. et al. TFEB safeguards trophoblast syncytialization in humans and mice. Proc. Natl. Acad. Sci. USA. 2024; 121(28): e2404062121. https://dx.doi.org/10.1073/pnas.2404062121
  41. Nakashima A., Cheng S.B., Ikawa M., Yoshimori T., Huber W.J., Menon R. et al. Evidence for lysosomal biogenesis proteome defect and impaired autophagy in preeclampsia. Autophagy. 2020; 16(10): 1771-85. https://dx.doi.org/10.1080/15548627.2019.1707494
  42. Nakashima A., Tsuda S., Kusabiraki T., Aoki A., Ushijima A., Shima T. et al. Current understanding of autophagy in pregnancy. Int. J. Mol. Sci. 2019; 20(9): 2342. https://dx.doi.org/10.3390/ijms20092342
  43. Cheng S., Banerjee S., Daiello L.A., Nakashima A., Jash S., Huang Z. et al. Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease. Sci. Rep. 2021; 11: 15934. https://dx.doi.org/10.1038/s41598-021-95611-5
  44. Janelidze S., Mattsson N., Palmqvist S., Smith R., Beach T.G., Serrano G.E. et al. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat. Med. 2020; 26: 379-86. https://dx.doi.org/10.1038/s41591-020-0755-1
  45. Palmqvist S., Janelidze S., Quiroz Y.T., Zetterberg H., Lopera F., Stomrud E. et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020; 324(8): 772-81. https://dx.doi.org/10.1001/jama.2020.12134
  46. Fagiani F., Govoni S., Racchi M., Lanni C. The Peptidyl-prolyl isomerase Pin1 in neuronal signaling: from neurodevelopment to neurodegeneration. Mol. Neurobiol. 2021; 58(3): 1062-73. https://dx.doi.org/10.1007/s12035-020-02179-8
  47. Sedov I., Khaibrakhmanova D. Molecular mechanisms of inhibition of protein amyloid fibril formation: evidence and perspectives based on kinetic models. Int. J. Mol. Sci. 2022; 23(21): 13428. https://dx.doi.org/10.3390/ijms232113428
  48. Al-Hilaly Y.K., Rickard J.E., Simpson M., Storey J.M.D., Harrington C.R., Wischik C.M. et al. A key region of Tau that is able to drive assembly and modulate inhibition by Hydromethylthionine. J. Mol. Biol. 2025; 437(17): 169231. https://dx.doi.org/10.1016/j.jmb.2025.169231
  49. Сидорова И.С., Манагадзе И.Д. Современные представления о преэклампсии с учетом роли нейронспецифических белков головного мозга плода. Акушерство и гинекология. 2025; 1: 5-11. https://dx.doi.org/10.18565/aig.2024.221 [Sidorova I.S., Managadze I.J. Current understanding of preeclampsia with regard to the role of fetal brain neuron-specific proteins. Obstetrics and Gynecology. 2025; (1): 5-11 (in Russian). https://dx.doi.org/10.18565/aig.2024.221].
  50. Сидорова И.С., Манагадзе И.Д. Сущность преэклампсии и возможности ее прекращения. Акушерство и гинекология. 2026; 1: 5-11. https://dx.doi.org/10.18565/aig.2025.223 [Sidorova I.S., Managadze I.J. The essence of preeclampsia and the possibility of its termination. Obstetrics and Gynecology. 2026; (1): 5-11 (in Russian). https://dx.doi.org/10.18565/aig.2025.223].
  51. Сидорова И.С., Манагадзе И.Д. Современная концепция развития преэклампсии: новые данные. Акушерство и гинекология. 2025; 2: 5-13. https://dx.doi.org/10.18565/aig.2024.272 [Sidorova I.S., Managadze I.J. Modern concept of the development of preeclampsia: new data. Obstetrics and Gynecology. 2025; (2): 5-13 (in Russian). https://dx.doi.org/10.18565aig.2024.272].

Received 28.01.2026

Accepted 18.05.2026

About the Authors

Iraida S. Sidorova, Dr. Med. Sci., Professor, Academician of the RAS, Merited Scholar of the Russian Federation, Merited Doctor of the Russian Federation, Professor at the Department of Obstetrics and Gynecology No. 1, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
(Sechenov University), 119991, Russia, Moscow, Trubetskaya str. 8, bld. 2, +7(499)248-67-29, sidorovais@yandex.ru, https://orcid.org/0000-0003-2209-8662
Andrey V. Murashko, Dr. Med. Sci., Professor, Professor at the Department of Obstetrics and Gynecology No 1, Institute of Clinical Medicine, I.M.Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str. 8, bld. 2, +7(499)248-67-29, murashkoa@mail.ru, https://orcid.org/0000-0003-0663-2909
Ioanna D. Managadze, Resident and PhD student at the Department of Obstetrics and Gynecology No. 1, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), 119991, Russia, Moscow, Trubetskaya str. 8, bld. 2, +7(499)248-67-29, ktb1966@mail.ru,
https://orcid.org/0000-0001-8745-9372
Corresponding author: Ioanna D. Managadze, ktb1966@mail.ru

Similar Articles

№5 / 2025
Nikitina N.A., Sidorova I.S., Amiraslanova N.I., Ageev M.B., Gololobova M.N.
Placental programming of neuropsychiatric disorders. Postnatal neurological consequences of preeclampsia
№7 / 2024
Belokrinitskaya T.E., Frolova N.I., Kargina D.S., Zolotukhina А.О., Agarkova М.А.
Severe preeclampsia and HELLP syndrome at 18 weeks gestation
№9 / 2024
Tyutyunnik V.L., Mirzabekova D.D., Mikhailova O.I., Kan N.E., Krasnyi A.M.
Correlation of perinatal outcomes in preeclampsia with the dynamics of CD16+ monocyte content in peripheral blood
№1 / 2025
Sidorova I.S., Managadze I.J.
Current understanding of preeclampsia with regard to the role of fetal brain neuronspecific proteins
№5 / 2026
Romanov A.Yu., Arfa M., Dolgushina N.V.
Pregnancy course and perinatal outcomes in women undergoing assisted reproductive technology with donor oocytes
By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.