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

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.

Fig. 1

Dot plot of relative gene expression of CDK10 (a), CDK11 (b), FOXO1 (c), and FOXO3 (d) of each sample in each of the brain regions (cerebellum and auditory cortex) and groups (Alzheimer's and control). *Difference between groups by Student's t-test for independent samples with p-value < 0.05

Fig. 2

Correlation of gene expression between genes of the same family by the Spearman’s test, considering brain region (cerebellum or auditory cortex) and AD vs control groups. a CDK10 and CDK11 in cerebellum. b FOXO1 and FOXO3 in the cerebellum. c CDK10 and CDK11 in the auditory cortex. d FOXO1 and FOXO3 in the auditory cortex in general analysis and by group. *Significant correlation by the Spearman’s test for p ≤ 0.05