Decreased Serum VEGF and TGF-Β1 Levels in Advanced Alzheimer's Patients; a preliminary study

Yıl 2024, Sayı: 2, 55 - 65, 30.09.2024

Ender Kaya , Durmuş Ayan , Esma Özmen , Seyyid Mehmet Bulut , İsmail Sarı , Serpil Erşan

Öz

Aim: This study aimed to investigate Vascular endothelial growth factor (VEGF) and Transforming growth factor beta 1(TGF-β1) levels in advanced Alzheimer's disease (AD).
Materials and Methods: A total of 60 participants were evaluated within the scope of the study. 30 of them constituted the patient group and 30 constituted the control group. VEGF and TGF-β1 levels in serum samples of the patient and control groups were measured by Enzyme-Linked Immunosorbent Assay (ELISA).
Results: In the AD group, serum VEGF levels were found to be statistically significantly lower than in the control group (1373.66±486.07 ng/L vs. 986.27±261.44 ng/L, p<0.001). TGFβ-1 levels were also found to be significantly decreased in the AH group compared to the control group (21.26±3.77 ng/ml vs. 24.63±2.73 ng/ml, p<0.001).
Conclusion: Our findings suggest that the decrease in VEGF and TGF-β1 levels in the AD group may be related to the disease. However, more comprehensive and large-scale studies are needed.

Anahtar Kelimeler

Alzheimer disease, VEGF, TGF-β1

İleri Alzheimer Hastalarında Azalmış Serum VEGF ve TGF-Β1 Seviyeleri; bir ön çalışma

Öz

Amaç: Bu araştırmada ileri evre Alzheimer hastalığında (AH) VEGF (Vasküler Endotelyal Büyüme Faktörü) ve TGF-β1 (Dönüştürücü Büyüme Faktörü-Beta 1) seviyelerinin incelenmesi amaçlanmıştır.
Gereç ve Yöntemler: Çalışma kapsamında toplam 60 katılımcı değerlendirilmiştir. Bunların 30'u hasta grubunu, 30'u ise kontrol grubunu oluşturmaktadır. Hasta ve kontrol grubuna ait serum örneklerinde VEGF ve TGF-β1 düzeyleri (ELISA) yöntemiyle ölçülmüştür.
Bulgular: AH grubunda, serum VEGF düzeyleri kontrol grubuna göre istatistiksel olarak anlamlı düzeyde düşük bulunmuştur (1373,66±486,07 ng/L'e karşılık 986,27±261,44 ng/L, p<0,001). TGFβ-1 düzeylerinin de AH grubunda kontrol grubuna göre önemli ölçüde azaldığı tespit edilmiştir (21,26±3,77 ng/ml'e karşılık 24,63±2,73 ng/ml, p<0,001).
Sonuç: Bulgularımız, AH grubunda VEGF ve TGF-β1 düzeylerindeki azalmanın hastalıkla ilişkili olabileceğini göstermektedir, ancak daha kapsamlı ve geniş katılımlı çalışmalara ihtiyaç olduğu düşünülmektedir.

Anahtar Kelimeler

Alzheimer hastalığı, VEGF, TGF-β1

Kaynakça

• Keleş E, Özalevli S. Alzheimer hastalığı ve tedavi yaklaşımları. İKÇÜSBFD 2018;3(2):39-42.
• Odabaşı MD, Tüylü Küçükkılınç ZT. Alzheimer hastalığı tedavisindeki güncel yaklaşımlar. HUJPHARM 2021;41(4):266-80.
• Mantzavinos V, Alexiou A. Biomarkers for Alzheimer’s disease diagnosis. Curr Alzheimer Res 2017;14(11):1149-1154. doi: 10.2174/1567205014666170203125942.
• Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: Targeting the Cholinergic system. Curr Neuropharmacol 2016;14(1):101-15. doi: 10.2174/1570159x13666150716165726.
• Aydın S, Taşyürek M, Öztürk C. MR Görüntülerinde evrişimli sinir ağlar kullanılarak Alzheimer hastalık tespiti. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi 2023; 39(3): 357-68.
• ten Dijke P, Hill CS. New insights into TGF-beta-Smad signalling. Trends Biochem Sci 2004;29(5):265-73. doi: 10.1016/j.tibs.2004.03.008.
• Şemsi R, Dinçel AS. Yaşın tükürük Transforme Edici Büyüme Faktör Beta (TGF-β) düzeyleri üzerindeki etkisi. Tıp Fakültesi Klinikleri Dergisi 2021; 4(3): 127-33. Li MO, Wan YY, Sanjabi S, Robertson AKL, Flavell RA. Transforming growth factor-Β regulation of ımmune responses. Annu Rev Immunol 2006;24:99-146. doi: 10.1146/annurev.immunol.24.021605.090737.
• Tesseur I, Zou K, Esposito L, Bard F, Berber E. et al. Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology. J Clin Invest 2006;116(11):3060-9. doi: 10.1172/JCI27341.
• Tesseur I, Nguyen A, Chang B, Li L, Woodling NS. et al. Deficiency in neuronal TGF-β signaling leads to nigrostriatal degeneration and activation of TGF-β signaling protects against MPTP neurotoxicity in mice. J Neurosci 2017;37(17):4584-4592. doi: 10.1523/JNEUROSCI.2952-16.2017.
• Bayram N, Y Karakan, M Uyar, B Ozyurt, A Filiz. Vascular endothelial growth factor in pleural effusions and correlation with radiologic and biochemical parameters. Niger J Clin Pract 2018;21(1):59-62. doi: 10.4103/njcp.njcp_370_16.
• Lladó J, Tolosa L, Olmos G. Cellular and molecular mechanisms involved in the neuroprotective effects of VEGF on motoneurons. Front Cell Neurosci 2013;7:181. doi: 10.3389/fncel.2013.00181.
• Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res 2000;55:15-35; discussion 35-6.
• Dai W, Lopez OL, Carmichael OT, Becker JT, Kuller LH. et al. Mild cognitive impairment and Alzheimer disease: Patterns of altered cerebral blood flow at MR imaging. Radiology 2009;250(3):856-66. doi: 10.1148/radiol.2503080751.
• Bracko O, Cruz Hernández JC, Park L, Nishimura N, Schaffer CB. Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease. J Cereb Blood Flow Metab 2021;41(7):1501-1516. doi: 10.1177/0271678X20982383.
• Ali M, Bracko O. VEGF paradoxically reduces cerebral blood flow in Alzheimer’s disease mice. Neurosci Insights 2022;17:26331055221109254. doi: 10.1177/26331055221109254.
• Huang L, Jia J, Liu R. Decreased serum levels of the angiogenic factors VEGF and TGF-β1 in Alzheimer’s disease and amnestic mild cognitive impairment. Neurosci Lett 2013;550:60-3. doi: 10.1016/j.neulet.2013.06.031.
• Lange C, Storkebaum E, de Almodóvar CR, Dewerchin M, Carmeliet P. Vascular endothelial growth factor: A neurovascular target in neurological diseases. Nat Rev Neurol 2016;12(8):439-54. doi: 10.1038/nrneurol.2016.88.
• Silva, Angelica Miki Stein, Gomes F, Andre Veloso Rueda, Camarini R, et al. Circulating levels of vascular endothelial growth factor in patients with Alzheimer’s disease: A case-control study. Behav Brain Res 2023;437:114126. doi: 10.1016/j.bbr.2022.114126.
• Sun Y, Jin K, Xie L, Childs J, Mao XO, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 2003;111(12):1843-51. doi: 10.1172/JCI17977.
• S.S. Zakariaee, Naderi N, Azizi E. Association of vascular endothelial growth factor levels with risk of Alzheimer’s disease: A systematic review and meta-analysis. J Prev Alzheimers Dis 2024;11(3):721-729. doi: 10.14283/jpad.2024.
• Jung J, Kim S, Yoon K, Moon Y, Roh D, et al. The Effect of depression on serum VEGF level in Alzheimer’s disease. Dis Markers 2015;2015:742612. doi: 10.1155/2015/742612.
• Mateo I, Llorca J, Infante J, Rodríguez-Rodríguez E, Fernández-Viadero C, et al. Low serum VEGF levels are associated with Alzheimer’s disease. Acta Neurol Scand 2007;116(1):56-8. doi: 10.1111/j.1600-0404.2006.00775.x.
• Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease: A double-edged sword. Neuron 2002;35(3):419-32. doi: 10.1016/s0896-6273(02)00794-8.
• Su C, Miao J, Guo J. The relationship between TGF-β1 and cognitive function in the brain. Brain Res Bull 2023:205:110820. doi: 10.1016/j.brainresbull.2023.110820.
• Chen JH, Ke KF, Lu JH, Qiu YH, Peng YP. Protection of TGF-β1 against neuroinflammation and neurodegeneration in Aβ1-42-induced Alzheimer's disease model rats. PLoS One 2015;10(2):e0116549. doi: 10.1371/journal.pone.0116549.
• Lesné S, Docagne F, GabrielC, Liot G, Lahiri DK, et al. Transforming growth factor-beta 1 potentiates amyloid-beta generation in astrocytes and in transgenic mice. J Biol Chem 2003;278(20):18408-18. doi: 10.1074/jbc.M300819200.
• Zetterberg H, Andreasen N, Blennow K. Increased cerebrospinal fluid levels of transforming growth factor-β1 in Alzheimer’s disease. Neurosci Lett 2004;367(2):194-6. doi: 10.1016/j.neulet.2004.06.001.
• Vivien D, Ali C. Transforming growth factor-β signalling in brain disorders. Cytokine Growth Factor Rev 2006:121-8. doi: 10.1016/j.cytogfr.2005.09.011.
• Mahoney ER, Dumitrescu L, Moore AM, Cambronero FE, De Jager PL, et al. Brain expression of the vascular endothelial growth factor gene family in cognitive aging and Alzheimer’s disease. Mol Psychiatry 2021;26(3):888-896. doi: 10.1038/s41380-019-0458-5.
• Boer K, Troost D, Wim G. M. Spliet, Peter, Gorter JA, et al. Cellular distribution of vascular endothelial growth factor A (VEGFA) and B (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB. Acta Neuropathol 2008;115(6):683-96. doi: 10.1007/s00401-008-0354-6.
• Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer. 2008;8(12):942-56. doi: 10.1038/nrc2524.
• Wang S, Qu Y, Fang X, Ding Q, Zhao H, et al. Decorin: a potential therapeutic candidate for ligamentum flavum hypertrophy by antagonizing TGF-β1. Exp Mol Med 2023;55(7):1413-1423. doi: 10.1038/s12276-023-01023-y.
• Zhang Y, Pan Y, Liu Y, Li X, Tang L, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition. Stem Cell Res Ther 2021;12(1):434. doi: 10.1186/s13287-021-02517-0.
• Nicholas SE, Choi AJ, Lam TN, Basu SK, Mandal N, Karamichos D. Potentiation of Sphingolipids and TGF-β in the human corneal stroma reveals intricate signaling pathway crosstalks. Exp Eye Res 2023;231:109487. doi: 10.1016/j.exer.2023.109487.