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The Role of Changes in the Expression of Inflammation-Associated Genes in Cerebral Small Vessel Disease with Cognitive Impairments

  • Clinical Presentation and Treatment of Nervous and Mental Diseases
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Objectives. To clarify the role of changes in the expression of inflammation-associated genes in cerebral small vessel disease (cSVD). Materials and methods. A total of 44 patients with cSVD (mean age 61.4 ± 9.2 years) and 11 volunteers (mean age 57.3 ± 9.7 years) were investigated. Gene expression was assessed using a custom NanoString nCounter panel of 58 inflammation-associated genes and four reference genes. The gene set was formed on the basis of convergent results from genome-wide association studies (GWAS) in cSVD and Alzheimer’s disease and circulating markers associated with vascular wall and brain damage in cSVD. RNA was isolated from blood leukocytes and analyzed using the nCounter Analysis System, with subsequent analysis in nSolver 4.0. Results were verified by real-time PCR. Results. Patients with cSVD, as compared with controls, had significantly lower levels of expression of BIN1 (log2FC = –1.272; p = 0.039) and VEGFA (log2FC = = –1.441; p = 0.038), which showed predictive ability for cSVD. The threshold value of BIN1 expression was 5.76 U (sensitivity 73%, specificity 75%), and that of VEGFA was 9.27 U (sensitivity 64%, specificity 86%). Decreased expression of VEGFA (p = 0.011), VEGFC (p = 0.017), and CD2AP (p = 0.044) was associated with clinically significant cognitive impairment. A significant direct correlation between Montreal Cognitive Assessment Scale test results and VEGFC expression was found; delayed memory test results correlated with BIN1 and VEGFC expression. Conclusions. The ability to predict the development of cSVD from low BIN1 and VEGFA expression levels and the association between clinically significant cognitive impairments with low VEGFA and VEGFC indicate their importance in the development and progression of the disease. The demonstrated significance of these genes in the pathogenesis of Alzheimer’s disease indicates that similar changes in their expression profile in cSVD may be among the conditions for the comorbidity of the two pathologies.

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References

  1. Gorelick, P. B., Scuteri, A., Black, S. E., et al., “Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association,” Stroke, 42, No. 9, 2672–2713 (2011), https://doi.org/10.1161/str.0b013e3182299496.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wardlaw, J. M., Smith, C., and Dichgans, M., “Small vessel disease: mechanisms and clinical implications,” Lancet Neurol., 18, No. 7, 684–696 (2019), https://doi.org/10.1016/s1474-4422(19)30079-1.

    Article  PubMed  Google Scholar 

  3. Toledo, J. B., Arnold, S. E., Raible, K., et al., “Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre,” Brain, 136, No. 9, 2697–2706 (2013), https://doi.org/10.1093/brain/awt188.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kapasi, A., DeCarli, C., and Schneider, J. A., “Impact of multiple pathologies on the threshold for clinically overt dementia,” Acta Neuropathol., 134, No. 2, 171–186 (2017), https://doi.org/10.1007/s00401-017-1717-7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jellinger, K. A. and Attems, J., “Neuropathology and general autopsy findings in nondemented aged subjects,” Clin. Neuropathol., 31, No. 2, 87–98 (2012), https://doi.org/10.5414/np300418.

    Article  PubMed  Google Scholar 

  6. Love, S. and Miners, J. S., “Cerebrovascular disease in ageing and Alzheimer’s disease,” Acta Neuropathol., 131, No. 5, 645–658 (2016), https://doi.org/10.1007/s00401-015-1522-0.

    Article  CAS  PubMed  Google Scholar 

  7. Kim, H. W., Hong, J., and Jeon, J. C., “Cerebral small vessel disease and Alzheimer’s disease: A review,” Front. Neurol., 11, 927 (2020), https://doi.org/10.3389/fneur.2020.00927.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Low, A., Mak, E., Malpetti, M., et al., “In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer’s disease,” J. Neurol. Neurosurg. Psychiatry, 92, 45–52 (2021), https://doi.org/10.1136/jnnp-2020-323894.

    Article  Google Scholar 

  9. Wolters, F. J., Zonneveld, H. I., Hofman, A., et al., “Cerebral perfusion and the risk of dementia: A population-based study,” Circulation, 136, No. 8, 719–728 (2017), https://doi.org/10.1161/CIRCULATIONAHA.117.027448.

    Article  PubMed  Google Scholar 

  10. Montagne, A., Barnes, S. R., Sweeney, M. D., et al., “Blood–brain barrier breakdown in the aging human hippocampus,” Neuron, 85, No. 2, 296–302 (2015), https://doi.org/10.1016/j.neuron.2014.12.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tayler, H., Miners, J. S., Güzel Ö, et al., “Mediators of cerebral hypoperfusion and blood–brain barrier leakiness in Alzheimer’s disease, vascular dementia and mixed dementia,” Brain Pathol., 31, No. 4, e12935 (2021), https://doi.org/10.1111/bpa.12935.

  12. Fakhoury, M., “Microglia and astrocytes in Alzheimer’s disease: Implications for therapy,” Curr. Neuropharmacol., 16, No. 5, 508–518 (2018), https://doi.org/10.2174/1570159x15666170720095240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Poudel, P. and Park, S., “Recent advances in the treatment of Alzheimer’s disease using nanoparticle-based drug delivery systems,” Pharmaceutics, 14, No. 4, 835 (2022), https://doi.org/10.3390/Pharmaceutics14040835.

    Article  Google Scholar 

  14. Jian, B., Hu, M., Cai, W., et al., “Update of immunosenescence in cerebral small vessel disease,” Front. Immunol., 11, 585655 (2020), https://doi.org/10.3389/fimmu.2020.585655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kaiser, D., Weise, G., Möller, K., et al., “Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease,” Acta Neuropathol. Commun., 2, 169 (2014), https://doi.org/10.1186/s40478-014-0169-8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Farkas, E., Donka, G., de Vos, R. A. I., et al., “Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain,” Acta Neuropathol., 108, No. 1, 57–64 (2004), https://doi.org/10.1007/s00401-004-0864-9.

    Article  PubMed  Google Scholar 

  17. Jalal, F. Y., Yang, Y., Thompson, J., et al., “Myelin loss associated with neuroinflammation in hypertensive rats,” Stroke, 43, No. 4, 1115–1122 (2012), https://doi.org/10.1161/strokeaha.111.643080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Löffler, T., Flunkert, S., Havas, D., et al., “Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivo model of Alzheimer’s disease,” J. Neuroinflammation, 11, 84 (2014), https://doi.org/10.1186/1742-2094-11-84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nazem, A., Sankowski, R., Bacher, M., and Al-Abed, Y., “Rodent models of neuroinflammation for Alzheimer’s disease,” J. Neuroinflammation, 12, 74 (2015), https://doi.org/10.1186/s12974-015-0291-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Simpson, J. E., Fernando, M. S., Clark, L., et al., “White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses,” Neuropathol. Appl. Neurobiol., 33, No. 4, 410–419 (2007), https://doi.org/10.1111/j.1365-2990.2007.00828.x.

    Article  CAS  PubMed  Google Scholar 

  21. Gouw, A. A., Seewann, A., van der Flier, W. M., et al., “Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations,” J. Neurol. Neurosurg. Psychiatry, 82, No. 2, 126–135 (2011), https://doi.org/10.1136/jnnp.2009.204685.

    Article  PubMed  Google Scholar 

  22. Cribbs, D. H., Berchtold, N. C., Perreau, V., et al., “Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study,” J. Neuroinflammation, 9, 179 (2012), https://doi.org/10.1186/1742-2094-9-179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gomez-Nicola, D. and Boche, D., “Post-mortem analysis of neuroinflammatory changes in human Alzheimer’s disease,” Alzheimers Res. Ther., 7, No. 1, 42 (2015), https://doi.org/10.1186/s13195-015-0126-1.

  24. Wilcock, D. M., Hurban, J., Helman, A. M., et al., “Down syndrome individuals with Alzheimer’s disease have a distinct neuroinflammatory phenotype compared to sporadic Alzheimer’s disease,” Neurobiol. Aging, 36, No. 9, 2468–2474 (2015), https://doi.org/10.1016/j.Neurobiolaging.2015.05.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Walsh, J., Tozer, D. J., Sari, H., et al., “Microglial activation and blood–brain barrier permeability in cerebral small vessel disease,” Brain, 144, No. 5, 1361–1371 (2021), https://doi.org/10.1093/brain/awab003.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lagarde, J., Sarazin, M., and Bottlaender, M., “In vivo PET imaging of neuroinflammation in Alzheimer’s disease,” J. Neural Transm. (Vienna), 125, No. 5, 847–867 (2018), https://doi.org/10.1007/s00702-017-1731-x.

    Article  CAS  PubMed  Google Scholar 

  27. Zimmer, E. R., Leuzy, A., Benedet, A. L., et al., “Tracking neuroinflammation in Alzheimer’s disease: the role of positron emission tomography imaging,” J. Neuroinflammation, 11, 120 (2014), https://doi.org/10.1186/1742-2094-11-120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chandra, A., Valkimadi, P. E., Pagano, G., et al., “Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer’s disease and mild cognitive impairment,” Hum. Brain Mapp., 40, No. 18, 5424–5442 (2019), https://doi.org/10.1002/hbm.24782.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fornage, M., Adams, H. H., Bis, J. C., et al., “Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium,” Ann. Neurol., 69, No. 6, 928–939 (2011), https://doi.org/10.1002/ana.22403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haffner, C., Malik, R., and Dichgans, M., “Genetic factors in cerebral small vessel disease and their impact on Stroke and dementia,” J. Cereb. Blood Flow Metab., 36, No. 1, 158–171 (2016), https://doi.org/10.1038/jcbfm.2015.71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Verhaaren, B. F., Debette, S., Bis, J. C., and et al., “Multiethnic genome-wide association study of cerebral white matter hyperintensities on, MRI,” Circ. Cardiovasc. Genet., 8, No. 2, 398–409 (2015), https://doi.org/10.1161/CIRCGENETICS.114.000858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Traylor, M., Tozer, D. J., Croall, I. D., et al., “Genetic variation in PLEKHG1 is associated with white matter hyperintensities (n = = 11,226),” Neurology, 92, No. 8, 749–757 (2019), https://doi.org/10.1212/WNL.0000000000006952.

    Article  CAS  Google Scholar 

  33. Persyn, E., Hanscombe, K. B., Howson, J. M. M., et al., “Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants,” Nat. Commun., 11, No. 1, 2175 (2020), https://doi.org/10.1038/s41467-020-15932-3.

  34. Sargurupremraj, M., Suzuki, H., et al., “Cerebral small vessel disease genomics and its implications across the lifespan,” Nat. Commun., 11, No. 1, 6285 (2020), https://doi.org/10.1038/s41467-020-19111-2.

  35. Armstrong, N. J., Mather, K. A., Sargurupremraj, M., et al., “Common genetic variation indicates separate etiologies for periventricular and deep white matter hyperintensities,” Stroke, 51, 2111–2121 (2020), https://doi.org/10.1161/STROKEAHA.119.027544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Knol, M. J., Lu, D., Traylor, M., et al., “Association of common genetic variants with brain microbleeds: A genome-wide association study,” Neurology, 95, No. 24, 3331–3343 (2020), https://doi.org/10.1212/WNL.0000000000010852.

    Article  CAS  Google Scholar 

  37. Li, H. Q., Cai, W. J., Hou, X. H., and et al., “Genome-wide association study of cerebral microbleeds on MRI,” Neurotox. Res., 37, No. 1, 146–155 (2020), https://doi.org/10.1007/s12640-019-00073-3.

    Article  CAS  PubMed  Google Scholar 

  38. McQuade, A. and Blurton-Jones, M., “Microglia in Alzheimer’s disease: Exploring how genetics and phenotype influence risk,” J. Mol. Biol., 431, No. 9, 1805–1817 (2019), https://doi.org/10.1016/j.jmb.2019.01.045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Naj, A. C., Jun, G., Beecham, G. W., et al., “Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease,” Nat. Genet., 43, No. 5, 436–441 (2011), https://doi.org/10.1038/ng.801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bellenguez, C., Grenier-Boley, B., and Lambert, J. C., “Genetics of Alzheimer’s disease: where we are, and where we are going,” Curr. Opin. Neurobiol., 61, 40–48 (2020), https://doi.org/10.1016/j.conb.2019.11.024.

    Article  CAS  PubMed  Google Scholar 

  41. Kamboh, M. I., Barmada, M. M., Demirci, F. Y., et al., “Genome-wide association analysis of age-at-onset in Alzheimer’s disease,” Mol. Psychiatry, 17, No. 12, 1340–1346 (2012), https://doi.org/10.1038/mp.2011.135.

    Article  CAS  PubMed  Google Scholar 

  42. Lambert, J. C., Ibrahim-Verbaas, C. A., Harold, D., et al., “Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease,” Nat. Genet., 45, No. 12, 1452–1458 (2013), https://doi.org/10.1038/ng.2802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Almeida, J. F. F., Dos Santos, L. R., Trancozo, M., and de Paula, F., “Updated meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 variants in Alzheimer’s disease,” J. Mol. Neurosci., 64, No. 3, 471–477 (2018), https://doi.org/10.1007/s12031-018-1045-y.

    Article  CAS  PubMed  Google Scholar 

  44. Dörr, A., “Single-cell RNA-seq relates GWAS variants to disease risk,” Nat. Biotechnol, 40, No. 11, 1574 (2022), https://doi.org/10.1038/s41587-022-01570-1.

  45. Williams, B., Mancia, G., Spiering, W., et al., “2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH),” G. Ital. Cardiol. (Rome), 19, No. 11, Suppl. 1, 3–73 (2018), https://doi.org/10.1714/3026.30245.

  46. Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Association, Arlington, VA (2013), 5th ed.

  47. Traylor, M., Malik, R., Nalls, M. A., et al., “Genetic variation at 16q24.2 is associated with small vessel stroke,” Ann. Neurol., 81, No. 3, 383–394 (2017), https://doi.org/10.1002/ana.24840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Malik, R., Chauhan, G., Traylor, M., et al., “Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes,” Nat. Genet., 50, No. 4, 524–537 (2018), https://doi.org/10.1038/s41588-018-0058-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Marini, S., Devan, W. J., Radmanesh, F., et al., “17p12 Influences hematoma volume and outcome in spontaneous intracerebral hemorrhage,” Stroke, 49, No. 7, 1618–1625 (2018), https://doi.org/10.1161/STROKEAHA.117.020091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chung, J., Marini, S., Pera, J., et al., “Genome-wide association study of cerebral small vessel disease reveals established and novel loci,” Brain, 142, No. 10, 3176–3189 (2019), https://doi.org/10.1093/brain/awz233.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Traylor, M., Persyn, E., Tomppo, L., et al., “Genetic basis of lacunar Stroke: a pooled analysis of individual patient data and genome-wide association studies,” Lancet Neurol., 20, No. 5, 351–361 (2021), https://doi.org/10.1016/S1474-4422(21)00031-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rajani, R. M. and Williams, A., “Endothelial cell-oligodendrocyte interactions in small vessel disease and aging,” Clin. Sci (Lond.), 131, No. 5, 369–379 (2017), https://doi.org/10.1042/CS20160618.

    Article  PubMed  Google Scholar 

  53. Rouhl, R. P., Damoiseaux, J. G., Lodder, J., et al., “Vascular inflammation in cerebral small vessel disease,” Neurobiol. Aging, 33, No. 8, 1800–1806 (2012), https://doi.org/10.1016/j.neurobiolaging.2011.04.008.

    Article  CAS  PubMed  Google Scholar 

  54. Zeng, L., Wang, Y., Liu, J., et al., “Pro-inflammatory cytokine network in peripheral inflammation response to cerebral ischemia,” Neurosci. Lett., 548, 4–9 (2013), https://doi.org/10.1016/j.neulet.2013.04.037.

    Article  CAS  PubMed  Google Scholar 

  55. Wiseman, S., Marlborough, F., Doubal, F., et al., “Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis,” Cerebrovasc. Dis., 37, No. 1, 64–75 (2014), https://doi.org/10.1159/000356789.

    Article  CAS  PubMed  Google Scholar 

  56. Shoamanesh, A., Preis, S. R., Beiser, A. S., et al., “Inflammatory biomarkers, cerebral microbleeds, and small vessel disease: Framingham Heart Study,” Neurology, 84, No. 8, 825–832 (2015), https://doi.org/10.1212/WNL.0000000000001279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kuriyama, N., Mizuno, T., Kita, M., et al., “TGF-beta1 is associated with the progression of intracranial deep white matter lesions: a pilot study with 5 years of magnetic resonance imaging follow-up,” Neurol Res., 36, No. 1, 47–52 (2014), https://doi.org/10.1179/1743132813Y.0000000256.

    Article  CAS  PubMed  Google Scholar 

  58. Dobrynina, L. A., Shabalina, A. A., Zabitova, M. R., et al., “Tissue plasminogen activator and MRI signs of cerebral small vessel disease,” Brain Sci., 9, 266 (2019), https://doi.org/10.3390/brainsci9100266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dobrynina, L. A., Gnedovskaya, E. V., and Shabalina, A. A., et al., “Bioarkers and the mechanisms of early vessel wall damage,” Zh. Nevrol. Psikhiatr., 118, No. 12, Iss. 2, 23–32 (2018), https://doi.org/10.17116/jnevro201811812223.

  60. Tingley, D., Yamamoto, T., Hirose, K., et al., “Mediation: R package for causal mediation analysis,” J. Stat. Softw., 59, No. 5 (2014), https://doi.org/10.18637/jss.v059.i05.

  61. Chapuis, J., Hansmannel, F., Gistelinck, M., et al., “Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology,” Mol. Psychiatry, 18, No. 11, 1225–1234 (2013), https://doi.org/10.1038/mp.2013.1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Prokic, I., Cowling, B. S., and Laporte, J., “Amphiphysin 2 (BIN1) in physiology and diseases,” J. Mol. Med (Berl.), 92, No. 5, 453–463 (2014), https://doi.org/10.1007/s00109-014-1138-1.

    Article  CAS  PubMed  Google Scholar 

  63. Taga, M., Petyuk, V. A., White, C., et al., “BIN1 protein isoforms are differentially expressed in astrocytes, Neurons, and microglia: Neuronal and astrocyte BIN1 are implicated in tau pathology,” Mol. Neurodegener., 15, No. 1, 44 (2020), https://doi.org/10.1186/s13024-020-00387-3.

  64. De Rossi, P., Buggia-Prévot, V., Clayton, B. L., et al., “Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts,” Mol. Neurodegener., 11, No. 1, 59 (2016), https://doi.org/10.1186/s13024-016-0124-1.

  65. Sudwarts, A., Ramesha, S., Gao, T., et al., “BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia,” Mol. Neurodegener., 17, No. 1, 33 (2022), https://doi.org/10.1186/s13024-022-00535-x.

  66. Wang, H. F., Wan, Y., Hao, X. K., et al., “Bridging Integrator 1 (BIN1) genotypes mediate Alzheimer’s disease risk by altering neuronal degeneration,” J. Alzheimers Dis., 52, No. 1, 179–190 (2016), https://doi.org/10.3233/JAD-150972.

    Article  CAS  PubMed  Google Scholar 

  67. Miyagawa, T., Ebinuma, I., Morohashi, Y., et al., “BIN1 regulates BACE1 intracellular trafficking and amyloid-β production,” Hum. Mol. Genet., 25, No. 14, 2948–2958 (2016), https://doi.org/10.1093/hmg/ddw146.

    Article  CAS  PubMed  Google Scholar 

  68. Tan, M. S., Yu, J. T., and Tan, L., “Bridging integrator 1 (BIN1, form, function, and Alzheimer’s disease,” Trends Mol. Med., 19, No. 10, 594–603 (2013), https://doi.org/10.1016/j.molmed.2013.06.004.

    Article  CAS  PubMed  Google Scholar 

  69. Esmailzadeh, S., Huang, Y., Su, M. W., et al., “BIN1 tumor suppressor regulates Fas/Fas ligand-mediated apoptosis through c-FLIP in cutaneous T-cell lymphoma,” Leukemia, 29, No. 6, 1402–1413 (2015), https://doi.org/10.1038/leu.2015.9.

    Article  CAS  PubMed  Google Scholar 

  70. Glennon, E. B., Whitehouse, I. J., Miners, J. S., et al., “BIN1 is decreased in sporadic but not familial Alzheimer’s disease or in aging,” PLoS One, 8, No. 10, e78806 (2013), https://doi.org/10.1371/journal.pone.0078806.

    Article  CAS  Google Scholar 

  71. Marques-Coelho, D., Iohan L. Da C. C., Melo de Farias, A. R., et al., “Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human Brains,” NPJ Aging Mech. Dis., 7, No. 1, 2 (2021), https://doi.org/10.1038/s41514-020-00052-5.

  72. McKenzie, A. T., Moyon, S., Wang, M., et al., “Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer’s disease,” Mol. Neurodegener., 12, No. 1, 82 (2017), https://doi.org/10.1186/s13024-017-0219-3.

  73. Martiskainen, H., Helisalmi, S., Viswanathan, J., et al., “Effects of Alzheimer’s disease-associated risk loci on cerebrospinal fluid biomarkers and disease progression: a polygenic risk score approach,” J. Alzheimers Dis., 43, No. 2, 565–573 (2015), https://doi.org/10.3233/JAD-140777.

    Article  CAS  PubMed  Google Scholar 

  74. Hu, H., Tan, L., Bi, Y. L., et al., “Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease,” Transl. Psychiatry, 11, No. 1, 89 (2021), https://doi.org/10.1038/s41398-021-01218-9.

  75. Sun, L., Tan, M. S., Hu, N., et al., “Exploring the value of plasma BIN1 as a potential biomarker for Alzheimer’s disease,” J. Alzheimers Dis., 37, No. 2, 291–295 (2013), https://doi.org/10.3233/JAD-130392.

    Article  CAS  PubMed  Google Scholar 

  76. Sweeney, M. D., Zhao, Z., Montagne, A., et al., “Blood–brain barrier: From physiology to disease and back,” Physiol. Rev., 99, No. 1, 21–78 (2019), https://doi.org/10.1152/physrev.00050.2017.

    Article  CAS  PubMed  Google Scholar 

  77. Andrew, R. J., De Rossi, P., Nguyen, P., et al., “Reduction of the expression of the late-onset Alzheimer’s disease (AD) risk-factor BIN1 does not affect amyloid pathology in an AD mouse model,” J. Biol. Chem., 294, No. 12, 4477–4487 (2019), https://doi.org/10.1074/jbc.RA118.006379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Juul Rasmussen, I., Tybjærg-Hansen, A., Rasmussen, K. L., et al., “Blood–brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals,” Eur. J. Epidemiol., 34, No. 6, 579–590 (2019), https://doi.org/10.1007/s10654-019-00498-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Dobrynina, L. A., Gnedovskaya, E. V., and Sergeeva, A. N., et al., “MRI changes in the brain in asymptomatic first diagnosed arterial hypertension,” Ann. Klin. Eksperim. Nevrol., 10, No. 3, 25–32 (2016).

    Google Scholar 

  80. Zhang, C. E., Wong, S. M., Uiterwijk, R., et al., “Blood–brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging,” Brain Imaging Behav., 13, No. 2, 389–395 (2019), https://doi.org/10.1007/s11682-018-9855-7.

    Article  PubMed  Google Scholar 

  81. Shibuya, M., “Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases,” J. Biochem., 153, No. 1, 13–19 (2013), https://doi.org/10.1093/jb/mvs136.

    Article  CAS  PubMed  Google Scholar 

  82. Lange, C., Storkebaum, E., de Almodóvar, C. R., et al., “Vascular endothelial growth factor: a neurovascular target in neurological diseases,” Nat. Rev. Neurol., 12, No. 8, 439–454 (2016), https://doi.org/10.1038/nrneurol.2016.88.

    Article  CAS  PubMed  Google Scholar 

  83. Dobrynina, L. A., Gnedovskaya, E. V., and Zabitova, M. R., et al., “Clustering of diagnosed MRI signs of cerebral microangiopathy and its association with markers of inflammation and angiogenesis,” Zh. Nevrol. Psikhiatr., 120, No. 12, Iss. 2, 22–31 (2020), https://doi.org/10.17116/jnevro202012012222.

  84. Dobrynina, L. A., Zabitova, M. R., Shabalina, A. A., et al., “MRI types of cerebral small vessel disease and circulating markers of vascular wall damage,” Diagnostics (Basel), 10, No. 6, 354 (2020), https://doi.org/10.3390/diagnostics10060354.

    Article  CAS  Google Scholar 

  85. Miyamoto, N., Pham, L. D., Seo, J. H., et al., “Crosstalk between cerebral endothelium and oligodendrocyte,” Cell. Mol. Life Sci., 71, No. 6, 1055–1066 (2014), https://doi.org/10.1007/s00018-013-1488-9.

    Article  CAS  PubMed  Google Scholar 

  86. Martin, L., Bouvet, P., Chounlamountri, N., et al., “VEGF counteracts amyloid-β-induced synaptic dysfunction,” Cell Rep., 35, No. 6, 109121 (2021), https://doi.org/10.1016/j.celrep.2021.109121.

  87. Patel, N. S., Mathura, V. S., Bachmeier, C., et al., “Alzheimer’s beta-amyloid peptide blocks vascular endothelial growth factor mediated signaling via direct interaction with VEGFR-2,” J. Neurochem., 112, No. 1, 66–76 (2010), https://doi.org/10.1111/j.1471-4159.2009.06426.x.

    Article  CAS  PubMed  Google Scholar 

  88. Huang, L., Jia, J., and Liu, R., “Decreased serum levels of the angiogenic factors VEGF and TGF-β1 in Alzheimer’s disease and amnestic mild cognitive impairment,” Neurosci. Lett., 550, 60–63 (2013), https://doi.org/10.1016/j.neulet.2013.06.031.

    Article  CAS  PubMed  Google Scholar 

  89. Yin, Q., Ma, J., Han, X., et al., “Spatiotemporal variations of vascular endothelial growth factor in the brain of diabetic cognitive impairment,” Pharmacol. Res., 163, 105234 (2021), https://doi.org/10.1016/j.phrs.2020.105234.

    Article  CAS  PubMed  Google Scholar 

  90. Tian, Y., Zhao, M., Chen, Y., et al., “The underlying role of the glymphatic system and meningeal lymphatic vessels in cerebral small vessel disease,” Biomolecules, 12, No. 6, 748 (2022), https://doi.org/10.3390/biom12060748.

    Article  CAS  Google Scholar 

  91. Li, Q., Chen, Y., Feng, W., et al., “Drainage of senescent astrocytes from Brain via meningeal lymphatic routes,” Brain Behav. Immun., 103, 85–96 (2022), https://doi.org/10.1016/j.bbi.2022.04.005.

    Article  CAS  PubMed  Google Scholar 

  92. Song, E., Mao, T., Dong, H., et al., “VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours,” Nature, 577, No. 7792, 689–694 (2020), https://doi.org/10.1038/s41586-019-1912-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Brown, A., Amunts, A., Bai X-C, et al., “Structure of the large ribosomal subunit from human mitochondria,” Science, 346, No. 6210, 718–722 (2014), https://doi.org/10.1126/science.1258026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Boczonadi, V. and Horvath, R., “Mitochondria: impaired mitochondrial translation in human disease,” Int. J. Biochem. Cell. Biol., 48, 77–84 (2014), https://doi.org/10.1016/j.biocel.2013.12.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Fischer, M. T., Sharma, R., Lim, J. L., et al., “NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury,” Brain, 135, 886–899 (2012), https://doi.org/10.1093/brain/aws012.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Lopez, L. M., Hill, W. D., Harris, S. E., et al., “Genes from a translational analysis support a multifactorial nature of white matter hyperintensities,” Stroke, 46, 341–347 (2015), https://doi.org/10.1161/STROKEAHA.114.007649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Trigo, D., Vitória, J. J., and Silva, O. A. B., “Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration,” Neural Regen. Res., 18, No. 5, 991–995 (2023), https://doi.org/10.4103/1673-5374.355750.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Center of Neurology, Moscow, Russia

    L. A. Dobrynina, A. G. Makarova, A. A. Shabalina, A. G. Burmak, P. S. Shlapakova, K. V. Shamtieva, M. M. Tsypushtanova, V. V. Trubitsyna & E. V. Gnedovskaya

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  1. L. A. Dobrynina
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  2. A. G. Makarova
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  3. A. A. Shabalina
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  4. A. G. Burmak
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  5. P. S. Shlapakova
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  6. K. V. Shamtieva
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  8. V. V. Trubitsyna
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  9. E. V. Gnedovskaya
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Correspondence to A. G. Makarova.

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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 123, No. 9, pp. 58–68, September, 2023.

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Dobrynina, L.A., Makarova, A.G., Shabalina, A.A. et al. The Role of Changes in the Expression of Inflammation-Associated Genes in Cerebral Small Vessel Disease with Cognitive Impairments. Neurosci Behav Physi 54, 210–221 (2024). https://doi.org/10.1007/s11055-024-01587-w

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