CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer's Disease Encephalic Samples

Cell Mol Neurobiol. 2023 Aug;43(6):2953-2962. doi: 10.1007/s10571-023-01341-9. Epub 2023 Mar 29.

Abstract

Alzheimer's disease (AD) is a progressive neuroinflammatory and neurodegenerative disorder that affects different regions of the brain. Its pathophysiology includes the accumulation of β-amyloid protein, formation of neurofibrillary tangles, and inflammatory processes. Genetic factors are involved in the onset of AD, but they are not fully elucidated. Identification of gene expression in encephalic tissues of patients with AD may help elucidate its development. Our objectives were to characterize and compare the gene expression of CDK10, CDK11, FOXO1, and FOXO3 in encephalic tissue samples from AD patients and elderly controls, from the auditory cortex and cerebellum. RT-qPCR was used on samples from 82 individuals (45 with AD and 37 controls). We observed a statistically significant increase in CDK10 (p = 0.029*) and CDK11 (p = 0.048*) gene expression in the AD group compared to the control, which was most evident in the cerebellum. Furthermore, the Spearman test demonstrated the presence of a positive correlation of gene expression both in the auditory cortex in the AD group (r = 0.046/p = 0.004) and control group (r = 0.454/p = 0.005); and in the cerebellum in the AD group (r = 0.654 /p < 0.001). There was no statistically significant difference and correlation in the gene expression of FOXO1 and FOXO3 in the AD group and the control. In conclusion, CDK10 and CDK11 have high expression in AD patients compared to control, and they present a positive correlation of gene expression in the analyzed groups and tissues, which suggests that they play an important role in the pathogenesis of AD.

Keywords: Alzheimer-disease; CDKs; Dementia; FOXOs; Gene-expression.

MeSH terms

  • Aged
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Forkhead Box Protein O3 / genetics
  • Gene Expression
  • Humans
  • Neurofibrillary Tangles / metabolism

Substances

  • Amyloid beta-Peptides
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • CDK10 protein, human
  • Cyclin-Dependent Kinases