Localization of Thioredoxin-Interacting Protein in Aging and Alzheimer’s Disease Brains

Abstract

Thioredoxin-Interacting Protein (TXNIP) has been shown to have significant pathogenic roles in many human diseases, particularly those associated with diabetes and hyperglycemia. Its main mode of action is to sequester thioredoxins, resulting in enhanced oxidative stress. The aim of this study was to identify if cellular expression of TXNIP in human aged and Alzheimer’s disease (AD) brains correlated with pathological structures. This study employed fixed tissue sections and protein extracts of temporal cortex from AD and aged control brains. Studies employed light and fluorescent immunohistochemical techniques using the monoclonal antibody JY2 to TXNIP to identify cellular structures. Immunoblots were used to quantify relative amounts of TXNIP in brain protein extracts. The major finding was the identification of TXNIP immunoreactivity in selective neuronal populations and structures, particularly in non-AD brains. In AD brains, less neuronal TXNIP but increased numbers of TXNIP-positive plaque-associated microglia were observed. Immunoblot analyses showed no significant increase in levels of TXNIP protein in the AD samples tested. In conclusion, this study identified altered patterns of expression of TXNIP in human brains with progression of AD pathology.

Keywords

• oxidative stress
• inflammation
• inflammasome
• neuropathology
• immunohistochemistry
• human tissue