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

Abstract

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.