Abstract
Giriş: Galektin-3 (Gal-3), birçok biyolojik süreçte rol alan multifonksiyonel bir protein olup en önemli rolü akut ve kronik inflamasyondadır. İnflamasyon, ileri yaşta kognitif gerilemenin ve demansın gelişmesinde önemli bir role sahiptir. Bu çalışmanın amacı galektin-3’ün Alzheimer Hastalığı (AH) patogenezindeki inflamasyonun bir göstergesi olup olmadığının ve bir biyobelirteç olarak kullanılabilirliğinin araştırılmasıdır.
Yöntemler: Çalışmaya, 44 Alzheimer hastası ve 44 normal kognitif fonksiyonlu olmak üzere toplam 88 hasta alınmıştır. Bilinen akut veya kronik infeksiyon tanısı olan, kronik inflamatuar hastalığı bulunan hastalar, kanser hastaları ve galektin-3 düzeyini etkileyen romatolojik hastalığı bulunan hastalar dışlanmıştır.
Bulgular: Analizler sonucunda Alzheimer Hastalığı grubunun galektin-3 düzeyi, kontrol grubundan yüksek saptanmıştır. Ancak istatistiksel olarak anlamlı değildir. Global Detoriasyon Skalası (GDS) evrelemesine göre orta-şiddetli AH (GDS evre 6) grubundaki hastaların galektin-3 düzeyleri hafif-orta evredeki (GDS evre 4-5) hastalara göre istatistiksel olarak anlamlı şekilde yüksek saptanmıştır. Galektin-3 düzeyi ile sayı menzili ileri (r = -0,216 P = 0,043) ve geri (r = -0,233 P = 0,029) testi arasında ters yönde, düşük kuvvette, istatistiksel olarak anlamlı bir korelasyon saptanmıştır.
Sonuç: Bu çalışma, galektin-3'ün Alzheimer Hastalığı'nın patogenezinde inflamasyon ve oksidatif stres göstergesi olarak önemli bir rol oynadığını göstermektedir. Bu ilişki Alzheimer Hastalığı’nın şiddeti ile ilişkili görünmektedir. Ancak, bu ilişkiyi netleştirmek için daha fazla ve daha kapsamlı prospektif çalışmalara ihtiyaç vardır.
References
- Perkins P, Annegers JF, Doody RS, Cooke N, Aday L, Vernon SW. Incidence and prevalence of dementia in a multiethnic cohort of municipal retirees. Neurology 1997;49:44-50.
- Mudher A, Lovestone S. Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci 2002;25:22-6.
- Liu P-P, Xie Y, Meng X-Y, Kang J-S. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Target Ther 2019;4:29.
- Cankurtaran M, Yesil Y, Kuyumcu ME, et al. Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer's disease. J Alzheimers Dis 2013;33:1051-8.
- Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362:329-44.
- Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition--the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 2002;50:2041-56.
- Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015;14:388-405.
- Khan TK, Alkon DL. Peripheral biomarkers of Alzheimer's disease. J Alzheimers Dis 2015;44:729-44.
- Dumic J, Dabelic S, Flogel M. Galectin-3: An open-ended story. Biochim Biophys Acta 2006;1760:616-35.
- Trompet S, Jukema W, Mooijaart SP, et al. Genetic variation in galectin-3 gene associates with cognitive function at old age. Neurobiol Aging 2012;33:2232.e1-.e9.
- Verkerke H, Dias-Baruffi M, Cummings RD, Arthur CM, Stowell SR. Galectins: An ancient family of carbohydrate binding proteinscarbohydrate binding proteins (cbps) with modern functions. In: Stowell SR, Arthur CM, Cummings RD, editors. Galectins: Methods and protocols. New York, NY: Springer US; 2022. p. 1-40.
- Hara A, Niwa M, Noguchi K, et al. Galectin-3 as a next-generation biomarker for detecting early stage of various diseases. Biomolecules 2020;10:389.
- Wang X, Zhang S, Lin F, Chu W, Yue S. Elevated galectin-3 levels in the serum of patients with Alzheimer's disease. Am J Alzheimers Dis Other Demen 2013;30:729-32.
- Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev 2009;230:160-71.
- Liu FT. Regulatory roles of galectins in the immune response. Int Arch Allergy Immunol 2005;136:385-400.
- Liu FT, Hsu DK. The role of galectin-3 in promotion of the inflammatory response. Drug News Perspect 2007;20:455-60.
- Boza-Serrano A, Ruiz R, Sanchez-Varo R, et al. Galectin-3, a novel endogenous trem2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease. Acta Neuropathol 2019;138:251-73.
- Arik G, Varan HD, Yavuz BB, et al. Validation of katz index of independence in activities of daily living in Turkish older adults. Arch Gerontol Geriatr 2015;61:344-50.
- Isik EI, Yilmaz S, Uysal I, Basar S. Adaptation of the Lawton instrumental activities of daily living scale to Turkish: Validity and reliability study. Ann Geriatr Med Res 2020;24:35-40.
- Tozlu M, Cankurtaran M, Yavuz BB, et al. Functional disability in Alzheimer disease: A validation study of the Turkish version of the disability assessment for dementia scale. J Geriatr Psychiatry Neurol 2014;27:237-46.
- Eker E, Yaşar R, Ertan T, Güngen C. Standardize mini mental testin Türk toplumunda hafif demans tanısında geçerlik ve güvenilirliği. Türk Psikiyatri Dergisi 2002;13:273-81.
- Stähelin HB, Monsch AU, Spiegel R. Early diagnosis of dementia via a two-step screening and diagnostic procedure. Int Psychogeriatr 1997;9 Suppl 1:123-30.
- Selekler K, Cangoz B, Uluc S. Power of discrimination of montreal cognitive assessment (moca) scale in Turkish patients with mild cognitive impairement and Alzheimer's disease. Turkish Journal of Geriatrics 2010;13:166-71.
- Cangoz B, Karakoc E, Selekler K. Trail making test: Normative data for Turkish elderly population by age, sex and education. J Neurol Sci 2009;283:73-8.
- Bosgelmez S, Yildiz M, Yazici E, et al. Reliability and validity of the Turkish version of cognitive assessment interview (cai-tr). Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology 2015;25:365-80.
- Association AP. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, USA: American Psychiatric Association; 1994.
- McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. J Alzheimers Dis 1984;34:939-44.
- Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-9.
- Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-94.
- Sarikaya D, Halil M, Kuyumcu ME, et al. Mini nutritional assessment test long and short form are valid screening tools in Turkish older adults. Arch Gerontol Geriatr 2015;61:56-60.
- Ertan T, Eker E. Reliability, validity, and factor structure of the geriatric depression scale in Turkish elderly: Are there different factor structures for different cultures? Int Psychogeriatr 2000;12:163-72.
- Yazar T, Olgun Yazar H, Cihan M. Evaluation of serum galectin-3 levels at Alzheimer patients by stages: A preliminary report. Acta Neurol Belg 2021;121:949-54.
- Xu M-m, Zhou M-t, Li S-w, Zhen X-c, Yang S. Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: A glycoproteomic approach. J Neurosci Res 2021;99:1308-24.
- Nio-Kobayashi J. Tissue- and cell-specific localization of galectins, β-galactose-binding animal lectins, and their potential functions in health and disease. Anat Sci Int 2017;92:25-36.
- Ramos-Martínez E, Ramos-Martínez I, Sánchez-Betancourt I, et al. Association between galectin levels and neurodegenerative diseases: Systematic review and meta-analysis. Biomolecules 2022;12:1062.
- Campbell IL, Stalder AK, Chiang CS, et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 1997;2:125-9.
- Ho GJ, Drego R, Hakimian E, Masliah E. Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr Drug Targets Inflamm Allergy 2005;4:247-56.
Galectin-3, an Indicator of Inflammation and Oxidation, is Linked with the Severity of Alzheimer’s Disease
Abstract
Introduction: Galectin-3 (Gal-3) is a multifunctional protein implicated in various biological processes, but the best-known role for galectin-3 is in acute and chronic inflammation. Inflammation plays an essential role in developing cognitive decline and dementia in old age. This study aims to investigate if galectin-3 can be an indicator of inflammation in Alzheimer’s Disease (AD) pathogenesis and a feasible biomarker of the disease.
Methods: Forty-four Alzheimer’s Disease patients and 44 patients with normal cognitive function were enrolled in the study. Patients with known acute or chronic infections, chronic inflammatory diseases, cancer patients, and patients with rheumatological diseases affecting galectin-3 levels were excluded.
Results: Analysis revealed that the galectin-3 level of the AD group was higher than the control group. However, it was not statistically significant. According to the Global Deterioration Scale (GDS), the galectin-3 levels of patients in the moderately severe AD group (GDS stage 6) were significantly higher than the patients in the mild-moderate AD group (GDS stage 4-5). There was a significant weak negative correlation between galectin-3 levels and the Digit Span Forward (r = - 0.216, P = 0.043) and Backward (r = - 0.233, P = 0.029) tests.
Conclusion: This study suggests that galectin-3 may play a role as an indicator of inflammation and oxidative stress in the pathogenesis of Alzheimer's Disease. It appears to be associated with the severity of AD. However, further and more extensive prospective studies are needed to clarify the association.
References
- Perkins P, Annegers JF, Doody RS, Cooke N, Aday L, Vernon SW. Incidence and prevalence of dementia in a multiethnic cohort of municipal retirees. Neurology 1997;49:44-50.
- Mudher A, Lovestone S. Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci 2002;25:22-6.
- Liu P-P, Xie Y, Meng X-Y, Kang J-S. History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Target Ther 2019;4:29.
- Cankurtaran M, Yesil Y, Kuyumcu ME, et al. Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer's disease. J Alzheimers Dis 2013;33:1051-8.
- Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362:329-44.
- Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognition--the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 2002;50:2041-56.
- Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015;14:388-405.
- Khan TK, Alkon DL. Peripheral biomarkers of Alzheimer's disease. J Alzheimers Dis 2015;44:729-44.
- Dumic J, Dabelic S, Flogel M. Galectin-3: An open-ended story. Biochim Biophys Acta 2006;1760:616-35.
- Trompet S, Jukema W, Mooijaart SP, et al. Genetic variation in galectin-3 gene associates with cognitive function at old age. Neurobiol Aging 2012;33:2232.e1-.e9.
- Verkerke H, Dias-Baruffi M, Cummings RD, Arthur CM, Stowell SR. Galectins: An ancient family of carbohydrate binding proteinscarbohydrate binding proteins (cbps) with modern functions. In: Stowell SR, Arthur CM, Cummings RD, editors. Galectins: Methods and protocols. New York, NY: Springer US; 2022. p. 1-40.
- Hara A, Niwa M, Noguchi K, et al. Galectin-3 as a next-generation biomarker for detecting early stage of various diseases. Biomolecules 2020;10:389.
- Wang X, Zhang S, Lin F, Chu W, Yue S. Elevated galectin-3 levels in the serum of patients with Alzheimer's disease. Am J Alzheimers Dis Other Demen 2013;30:729-32.
- Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev 2009;230:160-71.
- Liu FT. Regulatory roles of galectins in the immune response. Int Arch Allergy Immunol 2005;136:385-400.
- Liu FT, Hsu DK. The role of galectin-3 in promotion of the inflammatory response. Drug News Perspect 2007;20:455-60.
- Boza-Serrano A, Ruiz R, Sanchez-Varo R, et al. Galectin-3, a novel endogenous trem2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease. Acta Neuropathol 2019;138:251-73.
- Arik G, Varan HD, Yavuz BB, et al. Validation of katz index of independence in activities of daily living in Turkish older adults. Arch Gerontol Geriatr 2015;61:344-50.
- Isik EI, Yilmaz S, Uysal I, Basar S. Adaptation of the Lawton instrumental activities of daily living scale to Turkish: Validity and reliability study. Ann Geriatr Med Res 2020;24:35-40.
- Tozlu M, Cankurtaran M, Yavuz BB, et al. Functional disability in Alzheimer disease: A validation study of the Turkish version of the disability assessment for dementia scale. J Geriatr Psychiatry Neurol 2014;27:237-46.
- Eker E, Yaşar R, Ertan T, Güngen C. Standardize mini mental testin Türk toplumunda hafif demans tanısında geçerlik ve güvenilirliği. Türk Psikiyatri Dergisi 2002;13:273-81.
- Stähelin HB, Monsch AU, Spiegel R. Early diagnosis of dementia via a two-step screening and diagnostic procedure. Int Psychogeriatr 1997;9 Suppl 1:123-30.
- Selekler K, Cangoz B, Uluc S. Power of discrimination of montreal cognitive assessment (moca) scale in Turkish patients with mild cognitive impairement and Alzheimer's disease. Turkish Journal of Geriatrics 2010;13:166-71.
- Cangoz B, Karakoc E, Selekler K. Trail making test: Normative data for Turkish elderly population by age, sex and education. J Neurol Sci 2009;283:73-8.
- Bosgelmez S, Yildiz M, Yazici E, et al. Reliability and validity of the Turkish version of cognitive assessment interview (cai-tr). Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology 2015;25:365-80.
- Association AP. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, USA: American Psychiatric Association; 1994.
- McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. J Alzheimers Dis 1984;34:939-44.
- Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136-9.
- Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-94.
- Sarikaya D, Halil M, Kuyumcu ME, et al. Mini nutritional assessment test long and short form are valid screening tools in Turkish older adults. Arch Gerontol Geriatr 2015;61:56-60.
- Ertan T, Eker E. Reliability, validity, and factor structure of the geriatric depression scale in Turkish elderly: Are there different factor structures for different cultures? Int Psychogeriatr 2000;12:163-72.
- Yazar T, Olgun Yazar H, Cihan M. Evaluation of serum galectin-3 levels at Alzheimer patients by stages: A preliminary report. Acta Neurol Belg 2021;121:949-54.
- Xu M-m, Zhou M-t, Li S-w, Zhen X-c, Yang S. Glycoproteins as diagnostic and prognostic biomarkers for neurodegenerative diseases: A glycoproteomic approach. J Neurosci Res 2021;99:1308-24.
- Nio-Kobayashi J. Tissue- and cell-specific localization of galectins, β-galactose-binding animal lectins, and their potential functions in health and disease. Anat Sci Int 2017;92:25-36.
- Ramos-Martínez E, Ramos-Martínez I, Sánchez-Betancourt I, et al. Association between galectin levels and neurodegenerative diseases: Systematic review and meta-analysis. Biomolecules 2022;12:1062.
- Campbell IL, Stalder AK, Chiang CS, et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 1997;2:125-9.
- Ho GJ, Drego R, Hakimian E, Masliah E. Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr Drug Targets Inflamm Allergy 2005;4:247-56.
Details
| Primary Language | English |
|---|---|
| Subjects | Geriatrics and Gerontology |
| Journal Section | Research Articles |
| Authors | |
| Early Pub Date | March 28, 2024 |
| Publication Date | March 28, 2024 |
| Submission Date | December 13, 2023 |
| Acceptance Date | February 22, 2024 |
| Published in Issue | Year 2024 Volume: 5 Issue: 1 |
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