Expression profiles of the Tau-associated genes GSk3β, CAPN1, and CDK5R1 in the brain cortex of aged female cynomolgus monkeys with cognitive impairment.

BACKGROUND

Alzheimer's disease (AD) is characterized by the buildup and aggregation of misfolded proteins in the brain, including amyloid-β (Aβ) and hyperphosphorylated tau. The hyperphosphorylation state of Tau protein plays an important role in the development of AD. Our previous studies developed and characterized the cynomolgus monkey as a spontaneous animal model of AD.

AIM: We demonstrated the validity of the model through experimental investigations of the relationship between cognitive decline and AD neuropathy. There is, however, little information about the expression of hyperphosphorylated tau-related genes in various brain areas in the cynomolgus monkey spontaneous AD model.

METHODS

In the present study, total RNA was extracted from archived cortex and hippocampus tissues from the brains of two groups of cynomolgus monkeys, adult (10-12 years old, n = 5) and aged (> 20 years old, n = 4). The expression of the tau-protein-associated genes kinase 3 beta, calpain 1, and cyclin-dependent kinase 5 regulatory subunit 1 was evaluated using RT-qPCR.

RESULTS

The expression of all three genes increased by up to fivefold in the cortical brain area of aged subjects compared with adults.

CONCLUSION

Our results add weight to the utility of cynomolgus macaques as a valid spontaneous model in translational preclinical research involving studies of the effect of aging on the formation of hyperphosphorylated tau protein, which causes AD-related lesions in the brain.