Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1 and Prolactin


Cite item

Full Text

Abstract

Background:Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.

Objective:This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.

Methods:Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.

Results:Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.

Conclusion:The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.

About the authors

Yeşim Olğun

Department of Psychiatry, Istanbul University-Cerrahpaşa

Author for correspondence.
Email: info@benthamscience.net

Cana Aksoy Poyraz

Department of Psychiatry, Istanbul University-Cerrahpaşa

Email: info@benthamscience.net

Melda Bozluolçay

Department of Neurology, Istanbul University-Cerrahpaşa

Email: info@benthamscience.net

Dildar Konukoğlu

Department of Medical Biochemistry, Istanbul University-Cerrahpaşa

Email: info@benthamscience.net

Burç Poyraz

Department of Psychiatry, Istanbul University-Cerrahpaşa

Email: info@benthamscience.net

References

  1. Gale SA, Acar D, Daffner KR. Dementia. Am J Med 2018; 131(10): 1161-9. doi: 10.1016/j.amjmed.2018.01.022 PMID: 29425707
  2. McGinnis S. Neuroimaging in neurodegenerative dementias. Semin Neurol 2013; 32(4): 347-60. doi: 10.1055/s-0032-1331808 PMID: 23361481
  3. Dark HE, Duggan MR, Walker KA. Plasma biomarkers for Alzheimer’s and related dementias: A review and outlook for clinical neuropsychology. Arch Clin Neuropsychol 2024; acae019. doi: 10.1093/arclin/acae019 PMID: 38520383
  4. Du Y, Wu HT, Qin XY, et al. Postmortem brain, cerebrospinal fluid and blood neurotrophic factor levels in alzheimer’s disease: a systematic review and meta-analysis. J Mol Neurosci 2018; 65(3): 289-300. doi: 10.1007/s12031-018-1100-8 PMID: 29956088
  5. Ng TKS, Ho CSH, Tam WWS, Kua EH, Ho RC. Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with alzheimer's disease (AD): a systematic review and meta-analysis. Int J Mol Sci 2019; 20(2): 257. doi: 10.3390/ijms20020257
  6. Tampi RR, Maksimowski M, Ahmed M, Tampi DJ. Oxytocin for frontotemporal dementia: a systematic review. Ther Adv Psychopharmacol 2017; 7(1): 48-53. doi: 10.1177/2045125316672574 PMID: 28101324
  7. Panaro MA, Benameur T, Porro C. Hypothalamic neuropeptide brain protection: focus on oxytocin. J Clin Med 2020; 9(5): 1534. doi: 10.3390/jcm9051534 PMID: 32438751
  8. Froemke RC, Young LJ. Oxytocin, neural plasticity and social behavior. Annu Rev Neurosci 2021; 44(1): 359-81. doi: 10.1146/annurev-neuro-102320-102847 PMID: 33823654
  9. Kirsch P. Oxytocin in the socioemotional brain: implications for psychiatric disorders. Dialogues Clin Neurosci 2015; 17(4): 463-76. doi: 10.31887/DCNS.2015.17.4/pkirsch PMID: 26869847
  10. Raskind MA, Peskind ER, Lampe TH, Risse SC, Taborsky GJ Jr, Dorsa D. Cerebrospinal fluid vasopressin, oxytocin, somatostatin and beta-endorphin in Alzheimer’s disease. Arch Gen Psychiatry 1986; 43(4): 382-8. doi: 10.1001/archpsyc.1986.01800040092013 PMID: 2869744
  11. Mazurek MF, Beal MF, Bird ED, Martin JB. Oxytocin in Alzheimer’s disease. Neurology 1987; 37(6): 1001-3. doi: 10.1212/WNL.37.6.1001 PMID: 3587615
  12. North WG, Harbaugh R, Reeder T. An evaluation of human neurophysin production in Alzheimer’s disease: Preliminary observations. Neurobiol Aging 1992; 13(2): 261-5. doi: 10.1016/0197-4580(92)90038-Y PMID: 1522943
  13. Johnson EG, Kuiper W, Ahmed RM, et al. Plasma oxytocin is not associated with social cognition or behavior in frontotemporal dementia and alzheimer’s disease syndromes. Dement Geriatr Cogn Disord 2022; 51(3): 241-8. doi: 10.1159/000525087 PMID: 35705005
  14. Figueiro-Silva J, Gruart A, Clayton KB, et al. Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity. J Neurosci 2015; 35(14): 5504-21. doi: 10.1523/JNEUROSCI.2548-14.2015 PMID: 25855168
  15. Abad MA, Enguita M, DeGregorio-Rocasolano N, Ferrer I, Trullas R. Neuronal pentraxin 1 contributes to the neuronal damage evoked by amyloid-beta and is overexpressed in dystrophic neurites in Alzheimer’s brain. J Neurosci 2006; 26(49): 12735-47. doi: 10.1523/JNEUROSCI.0575-06.2006 PMID: 17151277
  16. Ma QL, Teng E, Zuo X, et al. Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer’s disease. Neurobiol Dis 2018; 114: 120-8. doi: 10.1016/j.nbd.2018.02.014 PMID: 29501530
  17. Krasemann S, Madore C, Cialic R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 2017; 47(3): 566-581.e9. doi: 10.1016/j.immuni.2017.08.008 PMID: 28930663
  18. Jay TR, von Saucken VE, Landreth GE. TREM2 in Neurodegenerative Diseases. Mol Neurodegener 2017; 12(1): 56. doi: 10.1186/s13024-017-0197-5
  19. Bekris LM, Khrestian M, Dyne E, et al. Soluble TREM2 and biomarkers of central and peripheral inflammation in neurodegenerative disease. J Neuroimmunol 2018; 319: 19-27. doi: 10.1016/j.jneuroim.2018.03.003 PMID: 29685286
  20. Culjak M, Perkovic MN, Uzun S, et al. The Association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer’s Disease. Curr Alzheimer Res 2021; 17(11): 972-84. doi: 10.2174/1567205017666201130092427 PMID: 33256580
  21. Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol 2021; 17(3): 157-72. doi: 10.1038/s41582-020-00435-y PMID: 33318676
  22. Leung YY, Toledo JB, Nefedov A, et al. Identifying amyloid pathology–related cerebrospinal fluid biomarkers for Alzheimer’s disease in a multicohort study. Alzheimers Dement 2015; 1(3): 339-48. doi: 10.1016/j.dadm.2015.06.008 PMID: 26693175
  23. House A, Jones J. Increased response of serum prolactin to metoclopramide in senile dementia of Alzheimer type. Int J Geriatr Psychiat 1989; 4(5): 279-82. doi: 10.1002/gps.930040506
  24. Balldin J, Gottfries C-G, Karlsson I, Lindstedt G, Långström G, Wålinder J. Dexamethasone suppression test and serum prolactin in dementia disorders. Br J Psychiatry 1983; 143(3): 277-81. doi: 10.1192/bjp.143.3.277 PMID: 6626841
  25. Olğun Y, Aksoy Poyraz C, Bozluolçay M, Poyraz BÇ. Quantitative EEG in the differential diagnosis of dementia subtypes. J Geriatr Psychiatry Neurol 2024; 08919887241227410. doi: 10.1177/08919887241227410 PMID: 38217438
  26. Olğun Y, Aksoy Poyraz C, Bozluolçay M, Gündüz A, Poyraz BÇ. A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer’s disease, dementia with Lewy bodies and Frontotemporal dementia. Psychogeriatrics 2024; 24(2): 272-80. doi: 10.1111/psyg.13070 PMID: 38131520
  27. Jack CR Jr, Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 257-62. doi: 10.1016/j.jalz.2011.03.004 PMID: 21514247
  28. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies. Neurology 2017; 89(1): 88-100. doi: 10.1212/WNL.0000000000004058 PMID: 28592453
  29. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134(9): 2456-77. doi: 10.1093/brain/awr179 PMID: 21810890
  30. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76(11): 1006-14. doi: 10.1212/WNL.0b013e31821103e6 PMID: 21325651
  31. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". J Psychiatr Res 1975; 12(3): 189-98. doi: 10.1016/0022-3956(75)90026-6 PMID: 1202204
  32. Güngen C, Ertan T, Eker E, Yaşar R, Engı̇n F. Reliability and validity of the standardized Mini Mental State Examination in the diagnosis of mild dementia in Turkish population. Turk Psikiyatr Derg 2002; 13(4): 273-81. PMID: 12794644
  33. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993; 43(11): 2412-4. doi: 10.1212/WNL.43.11.2412-a PMID: 8232972
  34. Leber I, Otto M, Vandenberghe R. European Reference Network For Rare Neurologıcal Dıseases (ERN-RND), "Scale To Measure Frontotemporal Dementıa CDR® Dementia Staging Instrument Plus NACC FTLD Behavior & Language Domains," 2020. Available from: www.ern-rnd.eu
  35. Reisberg B, Ferris SH, de Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982; 139(9): 1136-9. doi: 10.1176/ajp.139.9.1136 PMID: 7114305
  36. Garcia Basalo MM, Fernandez MC, Ojea Quintana M, et al. ALBA Screening Instrument (ASI): A brief screening tool for Lewy Body Dementia. Arch Gerontol Geriatr 2017; 70: 67-75. doi: 10.1016/j.archger.2017.01.001 PMID: 28088604
  37. de Medeiros K, Robert P, Gauthier S, et al. The neuropsychiatric inventory-clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia. Int Psychogeriatr 2010; 22(6): 984-94. doi: 10.1017/S1041610210000876 PMID: 20594384
  38. Şahi̇n Cankurtaran E, Danişman M, Tutar H, Ulusoy Kaymak S. The reliability and validity of the turkish version of the neuro psychiatric inventory-clinician. Turk J Med Sci 2015; 45(5): 1087-93. doi: 10.3906/sag-1405-111 PMID: 26738352
  39. Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 2015; 6(6): 1164-78. doi: 10.5114/aoms.2015.56342 PMID: 26788077
  40. Gao L, Zhang Y, Sterling K, Song W. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Transl Neurodegener 2022; 11(1): 4. doi: 10.1186/s40035-022-00279-0 PMID: 35090576
  41. Xue B, Waseem SMA, Zhu Z, et al. Brain-derived neurotrophic factor: a connecting link between nutrition, lifestyle and alzheimer’s disease. Front Neurosci 2022; 16: 925991. doi: 10.3389/fnins.2022.925991 PMID: 35692417
  42. Angelucci F, Spalletta G, Iulio F, et al. Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) patients are characterized by increased BDNF serum levels. Curr Alzheimer Res 2010; 7(1): 15-20. doi: 10.2174/156720510790274473 PMID: 20205668
  43. Gómez de San José N, Massa F, Halbgebauer S, Oeckl P, Steinacker P, Otto M. Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration. J Neural Transm 2022; 129(2): 207-30. doi: 10.1007/s00702-021-02411-2 PMID: 34460014
  44. Ashton NJ, Suárez-Calvet M, Heslegrave A, et al. Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers. Alzheimers Res Ther 2019; 11(1): 94. doi: 10.1186/s13195-019-0545-5
  45. Suárez-Calvet M, Kleinberger G, Araque Caballero MÁ, et al. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers. EMBO Mol Med 2016; 8(5): 466-76. doi: 10.15252/emmm.201506123
  46. Heslegrave A, Heywood W, Paterson R, et al. Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease. Mol Neurodegener 2016; 11: 3. doi: 10.1186/s13024-016-0071-x
  47. Qin Q, Teng Z, Liu C, Li Q, Yin Y, Tang Y. TREM2, microglia and Alzheimer’s disease. Mech Ageing Dev 2021; 195: 111438. doi: 10.1016/j.mad.2021.111438 PMID: 33516818
  48. Woollacott IOC, Nicholas JM, Heslegrave A, et al. Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup. Alzheimers Res Ther 2018; 10(1): 79. doi: 10.1186/s13195-018-0405-8
  49. Shaftel SS, Griffin WS, O'Banion MK. The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J Neuroinflammat 2008; 5: 7. doi: 10.1186/1742-2094-5-7
  50. Uchida Y, Kan H, Sakurai K, Oishi K, Matsukawa N. Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias. Front Aging Neurosci 2023; 15: 1111448. doi: 10.3389/fnagi.2023.1111448

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers