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 and 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: rs10305420, rs6923761 and rs1800437.

RESULTS

rs10305420 genotypes were associated with increased odds for AD and PD development. rs10305420 and rs6923761 genotypes were significantly associated with Aβ ratio (p = 0.041 and p = 0.050), while rs6923761 was also associated with p-tau levels (p = 0.022). Finally, rs1800437 heterozygotes as well as carriers of at least one 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

and 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 and genetic variability may support the function of incretin receptors in neurodegeneration.