20.500.12556/DiRROS-29934 Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ42/40 ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration. Alzheimer's disease biomarker glucagon-like peptide 1 receptor glucose-dependent insulinotropic polypeptide Parkinson's disease polymorphism Alzheimerjeva bolezen biološki označevalec glukagonu podoben receptor peptid 1 od glukoze odvisen insulinotropni polipeptid Parkinsonova bolezen polimorfizem true false true Angleški jezik Slovenski jezik Neznano 2026-06-09 13:31:30 2026-06-09 13:31:30 2026-06-10 03:48:59 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 14. 11. 2024; str. 1-9 iss. 20, [article no.] e39157 Vol. 10 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8:577 2405-8440 10.1016/j.heliyon.2024.e39157 214994947 RAZ_Vogrinc_David_2024.pdf RAZ_Vogrinc_David_2024.pdf 1 67B044D97FA9F59D1773FFFDFF143122 1f95070c290a6a439319c3890bd735af65c20373cdaa962894294161d042ca9b e0c9ddec-63f6-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45079 https://www.cell.com/action/showPdf?pii=S2405-8440%2824%2915188-2 1 c3f26779-63f6-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45078 Univerzitetni klinični center Ljubljana 0 0 0