Guardians of Neurons: The Cntf Gene and Ciliary Neurotrophic Factor (CNTF) in the Genetic Landscape of Alzheimer’s Disease Neuroprotection

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Pirya Nangdev
Shamshad Bano
Gulzar Fatima
Hina Ayub


Background: Type II Diabetes Mellitus (Type II DM) is a complex systemic disorder that affects various organs and has been strongly associated with an increased risk of cognitive impairments, including dementia. The Ciliary Neurotrophic Factor (CNTF) gene is implicated in the pathophysiology of diabetes-induced cognitive decline, suggesting its potential as a biomarker for neurodegenerative diseases.

Objective: The primary objective of this study was to investigate the expression of the CNTF gene in diabetic patients with dementia and to evaluate its correlation with cognitive dysfunction.

Methods: A cohort of 88 diabetic dementia patients and 12 healthy controls was selected based on inclusion criteria. CNTF serum levels were measured using Chemiluminescent immunoassay (CLIA), and CNTF gene expression was assessed through real-time PCR. DNA was isolated using the QIAgen blood kit, followed by bisulfite DNA modification and Methylation Specific PCR for methylation profiling. Data analysis included comparative studies using GraphPad Prism 9.0 with statistical significance set at a p-value of <0.05.

Results: The study found that CNTF serum levels in diabetic dementia patients (n=88) were significantly lower at 4.98 µg/mL compared to 14.21 µg/mL in healthy controls (n=12). MMSE scores were also reduced in the patient cohort, averaging 10.98 versus 25.6 in controls. A notable decrease in CNTF gene expression was observed with a fold change of approximately 4.1 in diabetic dementia patients, indicating underexpression in this group.

Conclusion: CNTF gene expression is inversely correlated with cognitive function in diabetic patients, suggesting that CNTF could serve as a useful biomarker for the early detection of dementia in this population. The identification of this gene's role opens new avenues for targeted therapeutic interventions and enhances the understanding of dementia's etiology in diabetic patients.

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How to Cite
Nangdev, P., Bano, S., Fatima, G., & Ayub , H. (2024). Guardians of Neurons: The Cntf Gene and Ciliary Neurotrophic Factor (CNTF) in the Genetic Landscape of Alzheimer’s Disease Neuroprotection. Journal of Health and Rehabilitation Research, 4(1), 1691–1695.
Author Biographies

Pirya Nangdev, Liaquat University of Medical and Health Sciences LUMHS Jamshoro Sindh Pakistan.

M.Phil (Anatomy), MBBS, Lecturer, Department of Anatomy, Bilawal Medical College, Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro Sindh, Pakistan.

Shamshad Bano, Liaquat University of Medical and Health Sciences LUMHS Jamshoro Sindh Pakistan.

MBBS M.Phil Anatomy, Department of Anatomy, Bilawal Medical College, Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro Sindh, Pakistan.

Gulzar Fatima, Forman Christian College (A Chartered University) Lahore Pakistan.

M.Phil in Molecular pathology and genomics, Kauser Abdullah Malik School of Life Sciences, Forman Christian College (A Chartered University) Lahore, Pakistan.

Hina Ayub , Jeju National University

BS Zoology, MS in Advance Convergence Science and Technology PhD*, Department of Advanced Convergence Technology and Science, Jeju National University South Korea


Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008;88(11):1322-35.

Ehtewish H, Arredouani A, El-Agnaf O. Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline. Int J Mol Sci. 2022;23(11):6144.

Flores-Dorantes MT, Díaz-López YE, Gutiérrez-Aguilar R. Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases. Front Neurosci. 2020;14:863.

Taylor R. Insulin resistance and type 2 diabetes. Diabetes. 2012;61(4):778-9.

Rezende LF, Santos GJ, Santos-Silva JC, Carneiro EM, Boschero AC. Ciliary neurotrophic factor (CNTF) protects non-obese Swiss mice against type 2 diabetes by increasing beta cell mass and reducing insulin clearance. Diabetologia. 2012;55(5):1495-504.

Lemper M, De Groef S, Stangé G, Baeyens L, Heimberg H. A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia. Diabetologia. 2016;59(9):1948-58.

Silva S, Nitsch D, Fatumo S. Genome-wide association studies on coronary artery disease: A systematic review and implications for populations of different ancestries. PLoS One. 2023;18(11):e0294341.

Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022;55(1):31-55.

Kohlgruber A, Lynch L. Adipose tissue inflammation in the pathogenesis of type 2 diabetes. Curr Diab Rep. 2015;15(11):92.

Massaro AR, Soranzo C, Carnevale A. Cerebrospinal-fluid ciliary neurotrophic factor in neurological patients. Eur Neurol. 1997;37(4):243-6.

Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener. 2016;11(1):50.

Spinelli M, Fusco S, Grassi C. Brain Insulin Resistance and Hippocampal Plasticity: Mechanisms and Biomarkers of Cognitive Decline. Front Neurosci. 2019;13:788.

Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights. 2016;11:95-104.

Rajmohan R, Reddy PH. Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer's disease Neurons. J Alzheimers Dis. 2017;57(4):975-99.

Jackson RJ, Rudinskiy N, Herrmann AG, Croft S, Kim JM, Petrova V, Ramos-Rodriguez JJ, Pitstick R, Wegmann S, Garcia-Alloza M, Carlson GA, Hyman BT, Spires-Jones TL. Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease. Eur J Neurosci. 2016;44(12):3056-66.

Jiao F, Jiang D, Li Y, Mei J, Wang Q, Li X. Amyloidogenesis and Neurotrophic Dysfunction in Alzheimer's Disease: Do They have a Common Regulating Pathway? Cells. 2022;11(20):3201.

Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.

Guo Q, Li H, Cole AL, Hur JY, Li Y, Zheng H. Modeling Alzheimer's disease in mouse without mutant protein overexpression: cooperative and independent effects of Aβ and tau. PLoS One. 2013;8(11):e80706.

Benussi L, Binetti G, Ghidoni R. Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point? Front Neurosci. 2017;11:672.

Arosio B, D'Addario C, Gussago C, Casati M, Tedone E, Ferri E, Nicolini P, Rossi PD, Maccarrone M, Mari D. Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly. BioMed Res Int. 2014;2014:169203.