Araştırma Makalesi
Yıl 2025,
Cilt: 15 Sayı: 1, 77 - 85, 16.04.2025
Öz
Proje Numarası
Research Fund of Istanbul University TTU-2023-39857
Kaynakça
- 1. Guo T, Zhang D, Zeng Y, Huang TY , Xu H , Zhao Y. Molecular and cellular mechanisms underlYing the pathogenesis of Alzheimer’s disease. Mol Neurodegener 2020; 15: 1-37. google scholar
- 2. Park SA, Han SM, Kim CE. New fluid biomarkers tracking non-amYloid-p and non-tau pathologY in Alzheimer’s disease. Exp Mol Med 2020; 52: 556-68. google scholar
- 3. Fahed G, Aoun L, Zerdan MB, Allam S, Zerdan MB, Bouferraa Y. Metabolic sYndrome: updates on pathophYsiologY and management in 2021. Y İnt J Mol Sci 2022; 23: 786. google scholar
- 4. Al-KuraishY HM, Majid S. Jabir MS, AlbuhadilY AK, Al-Gareeb Aİ, Rafeeq MF. The link between metabolic sYndrome and Alzheimer disease: A mutual relationship and long rigorous investigation. Ageing Res Rev 2023; 91: 102084. google scholar
- 5. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et.al. NİA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14: 535-62. google scholar
- 6. Pais M, Martinez L, Ribeiro O, Loureiro J, Fernandez R, Valiengo L, et al. EarlY diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Braz J PsYchiatrY 2020; 42: 431-41. google scholar
- 7. Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, et al. Plasma phospho-tau181 increases with Alzheimer’s disease clinical severitY and is associated with tau- and amYloid-positron emission tomographY. Alzheimers Dement 2018; 14: 989-97. google scholar
- 8. Park JC, Han SH, Yi D, BYun MS, Lee JH, Jang S, et al. Plasma tau/amYloid-pl-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease. Brain 2019; 142: 771-86. google scholar
- 9. Tsai CL, Liang CS, Lee JT, Su MW, Lin CC, Chu HT, et al. Associations between plasma biomarkers and cognition in patients with Alzheimer’s disease and amnestic mild cognitive impairment: a cross-sectional and longitudinal studY. J Clin Med 2019; 8: 1893. google scholar
- 10. Jiang T, Gong PY, Tan MS, Xue X, Huang S, Zhou JS, et al. Soluble TREM1 concentrations are increased and positivelY correlated with total tau levels in the plasma of patients with Alzheimer’s disease. Aging Clin Exp Res 2019; 31: 1801-5. google scholar
- 11. Verberk İMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM, et al. Plasma amYloid as prescreener for the earliest alzheimer pathological changes. Ann Neurol 2018; 84: 648-58. google scholar
- 12. De Wolf F, Ghanbari M, Licher S, McRae-McKee K, Gras L, Weverling GJ, et al. Plasma tau, neuroflament light Chain and amYloid-p levels and risk of dementia; a population-based cohort studY. Brain 2020; 143: 1220-32. google scholar
- 13. Chiu MJ, Chen YF, Chen TF, Yang SY, Yang FP, Tseng TW, et al. Plasma tau as a window to the brain-negative associations with brain volume and memorY function in mild cognitive impairment and earlY Alzheimer’s disease. Hum Brain Mapp 2014; 35: 3132-42. google scholar
- 14. Mattsson N, Andreasson U, Zetterberg H, Blennow K. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 2017; 74: 557-66. google scholar
- 15. Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P, et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther 2018; 10: 71. google scholar
- 16. Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL, et al. The characterisation of subjective cognitive decline. Lancet Neurol 2020; 19: 271-8. google scholar
- 17. Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther 2015; 7: 74. google scholar
- 18. McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 2013; 126: 479-97. google scholar
- 19. Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Mânsson JE, et al. Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromolecular Med 2011; 13: 151-9. google scholar
- 20. Norden DM, Muccigrosso MM, Godbout JP. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, andneurodegenerative disease Neuropharmacology 2015; 96: 29-41. google scholar
- 21. Chiasserini D, Parnetti L, Andreasson U, Zetterberg H, Giannandrea D, Calabresi P, et al. CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer’s disease. J Alzheimer’s Dis 2010; 22: 1281-8. google scholar
- 22. Vidal-Pineiro D, Sorensen Q, Blennow K, Capogna E, Halaas NB, Idland AV, et al. Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults. Neurobiol Aging 2022; 116: 80-91. google scholar
- 23. Shioda N, Yabuki Y, Kobayashi Y, Onozato M, Owada Y, Fukunaga K. FABP3 protein promotes a-synuclein oligomerization Associated with 1-Methyl-1,2,3,6 tetrahydropiridine- induced neurotoxicity. J Biol Chem 2014; 289: 18957-65. google scholar
- 24. Armstrong RA. Risk factors for Alzheimer’s disease. Folia Neuropathol 2019; 57:87-105. google scholar
- 25. Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: The role of nutrient transporters. J Cereb Blood Flow Meta 2007; 27: 1766-91. google scholar
- 26. Jacob RJ, Fan X, Evans ML, Dziura J, Sherwin RS. Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: No evidence for protective adaptation by the blood brain barrier. Metabolism 2002; 51: 1522-4. google scholar
- 27. Tomlinson DR, Gardiner NJ. Glucose neurotoxicity. Nat Rev Neurosci 2008; 9:36-45. google scholar
- 28. Li S, Jin M, Zhang D, Yang T, Koeglsperger T, Fu H, et al. Environmental novelty activates beta2-adrenergic signaling to prevent the impairment of hippocampal LTP by Abeta oligomers. Neuron 2013; 77: 929-41. google scholar
- 29. Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjohann D, Moore C, et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol 2003; 60: 510-5. google scholar
- 30. Chakraborty A, de Wit NM, van der Flier WM, de Vries HE. The blood brain barrier in Alzheimer’s disease. Vascul Pharmacol 2017; 89: 12-8. google scholar
The Evaluation of Serum Total Tau, NFL, Neurogranin, YKL-40, and FABP-3 as Screening Biomarkers for Alzheimer’s Disease
Öz
Objective: Alzheimer’s disease (AD) is a neurodegenerative disorder that causes dementia and accounts for 50-75% of all cases. Since cerebrospinal fluid sampling (CSF) is an invasive procedure, there is a need for non- or less invasive alternatives to identify new biomarkers that reflect the underlying AD pathology.
Materials and Methods: Blood samples were obtained from 86 AD patients (33 mild, 29 moderate, and 24 severe AD) and 30 controls. Serum total tau, neurofilament light polypeptide (NFL), neurogranin, chitinase-3-like protein 1 (YKL-40), and fatty acid-binding protein 3 (FABP-3) were measured using enzymelinked immunosorbent assay (ELISA).
Results: Serum total tau and NFL levels were higher in AD patients compared to controls, whereas neurogranin, YKL-40, and FABP-3 levels remained unchanged. In the receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity for total tau alone (cut-off point: 71.5 pg/mL) were 79.1% and 76.7% (Area under the curve (AUC): 0.865; p<0.001), while the sensitivity and specificity for NFL alone (cut-off point: 1.835 pg/mL) were 66.3% and 66.7% (AUC: 0.693; p=0.002). When total tau and NFL were concomitantly evaluated, the AUC was 0.848 (p<0.001).
Conclusion: Alongside the established core AD biomarkers, serum total tau and NFL are promising biomarkers for AD, reflecting additional pathological changes during the disease.
Proje Numarası
Research Fund of Istanbul University TTU-2023-39857
Kaynakça
- 1. Guo T, Zhang D, Zeng Y, Huang TY , Xu H , Zhao Y. Molecular and cellular mechanisms underlYing the pathogenesis of Alzheimer’s disease. Mol Neurodegener 2020; 15: 1-37. google scholar
- 2. Park SA, Han SM, Kim CE. New fluid biomarkers tracking non-amYloid-p and non-tau pathologY in Alzheimer’s disease. Exp Mol Med 2020; 52: 556-68. google scholar
- 3. Fahed G, Aoun L, Zerdan MB, Allam S, Zerdan MB, Bouferraa Y. Metabolic sYndrome: updates on pathophYsiologY and management in 2021. Y İnt J Mol Sci 2022; 23: 786. google scholar
- 4. Al-KuraishY HM, Majid S. Jabir MS, AlbuhadilY AK, Al-Gareeb Aİ, Rafeeq MF. The link between metabolic sYndrome and Alzheimer disease: A mutual relationship and long rigorous investigation. Ageing Res Rev 2023; 91: 102084. google scholar
- 5. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et.al. NİA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14: 535-62. google scholar
- 6. Pais M, Martinez L, Ribeiro O, Loureiro J, Fernandez R, Valiengo L, et al. EarlY diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Braz J PsYchiatrY 2020; 42: 431-41. google scholar
- 7. Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, et al. Plasma phospho-tau181 increases with Alzheimer’s disease clinical severitY and is associated with tau- and amYloid-positron emission tomographY. Alzheimers Dement 2018; 14: 989-97. google scholar
- 8. Park JC, Han SH, Yi D, BYun MS, Lee JH, Jang S, et al. Plasma tau/amYloid-pl-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer’s disease. Brain 2019; 142: 771-86. google scholar
- 9. Tsai CL, Liang CS, Lee JT, Su MW, Lin CC, Chu HT, et al. Associations between plasma biomarkers and cognition in patients with Alzheimer’s disease and amnestic mild cognitive impairment: a cross-sectional and longitudinal studY. J Clin Med 2019; 8: 1893. google scholar
- 10. Jiang T, Gong PY, Tan MS, Xue X, Huang S, Zhou JS, et al. Soluble TREM1 concentrations are increased and positivelY correlated with total tau levels in the plasma of patients with Alzheimer’s disease. Aging Clin Exp Res 2019; 31: 1801-5. google scholar
- 11. Verberk İMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM, et al. Plasma amYloid as prescreener for the earliest alzheimer pathological changes. Ann Neurol 2018; 84: 648-58. google scholar
- 12. De Wolf F, Ghanbari M, Licher S, McRae-McKee K, Gras L, Weverling GJ, et al. Plasma tau, neuroflament light Chain and amYloid-p levels and risk of dementia; a population-based cohort studY. Brain 2020; 143: 1220-32. google scholar
- 13. Chiu MJ, Chen YF, Chen TF, Yang SY, Yang FP, Tseng TW, et al. Plasma tau as a window to the brain-negative associations with brain volume and memorY function in mild cognitive impairment and earlY Alzheimer’s disease. Hum Brain Mapp 2014; 35: 3132-42. google scholar
- 14. Mattsson N, Andreasson U, Zetterberg H, Blennow K. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 2017; 74: 557-66. google scholar
- 15. Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P, et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther 2018; 10: 71. google scholar
- 16. Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL, et al. The characterisation of subjective cognitive decline. Lancet Neurol 2020; 19: 271-8. google scholar
- 17. Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther 2015; 7: 74. google scholar
- 18. McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 2013; 126: 479-97. google scholar
- 19. Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Mânsson JE, et al. Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromolecular Med 2011; 13: 151-9. google scholar
- 20. Norden DM, Muccigrosso MM, Godbout JP. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, andneurodegenerative disease Neuropharmacology 2015; 96: 29-41. google scholar
- 21. Chiasserini D, Parnetti L, Andreasson U, Zetterberg H, Giannandrea D, Calabresi P, et al. CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer’s disease. J Alzheimer’s Dis 2010; 22: 1281-8. google scholar
- 22. Vidal-Pineiro D, Sorensen Q, Blennow K, Capogna E, Halaas NB, Idland AV, et al. Relationship between cerebrospinal fluid neurodegeneration biomarkers and temporal brain atrophy in cognitively healthy older adults. Neurobiol Aging 2022; 116: 80-91. google scholar
- 23. Shioda N, Yabuki Y, Kobayashi Y, Onozato M, Owada Y, Fukunaga K. FABP3 protein promotes a-synuclein oligomerization Associated with 1-Methyl-1,2,3,6 tetrahydropiridine- induced neurotoxicity. J Biol Chem 2014; 289: 18957-65. google scholar
- 24. Armstrong RA. Risk factors for Alzheimer’s disease. Folia Neuropathol 2019; 57:87-105. google scholar
- 25. Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: The role of nutrient transporters. J Cereb Blood Flow Meta 2007; 27: 1766-91. google scholar
- 26. Jacob RJ, Fan X, Evans ML, Dziura J, Sherwin RS. Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: No evidence for protective adaptation by the blood brain barrier. Metabolism 2002; 51: 1522-4. google scholar
- 27. Tomlinson DR, Gardiner NJ. Glucose neurotoxicity. Nat Rev Neurosci 2008; 9:36-45. google scholar
- 28. Li S, Jin M, Zhang D, Yang T, Koeglsperger T, Fu H, et al. Environmental novelty activates beta2-adrenergic signaling to prevent the impairment of hippocampal LTP by Abeta oligomers. Neuron 2013; 77: 929-41. google scholar
- 29. Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjohann D, Moore C, et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol 2003; 60: 510-5. google scholar
- 30. Chakraborty A, de Wit NM, van der Flier WM, de Vries HE. The blood brain barrier in Alzheimer’s disease. Vascul Pharmacol 2017; 89: 12-8. google scholar
Toplam 30 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri (Diğer) |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | Research Fund of Istanbul University TTU-2023-39857 |
| Yayımlanma Tarihi | 16 Nisan 2025 |
| Gönderilme Tarihi | 19 Kasım 2024 |
| Kabul Tarihi | 4 Mart 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 15 Sayı: 1 |
