Quantitative Cytochrome Oxidase Histochemistry: Applications in Human Alzheimer's Disease and Animal Models

Abstract

Quantitative cytochrome oxidase (CO) histochemistry provides an intracellular measure of oxidative energy metabolic capacity that can be used as a tool to evaluate brain functional changes. CO enzyme activity also has been shown to be catalytically abnormal in patients with Alzheimer's disease (AD). The application of CO histochemistry to postmortem AD and control human brains, as well as in comparative studies of murine models, is presented here, from the cellular to laminar to regional and multiregional levels of analysis. In AD cases and controls, we compared CO in 11 brain regions-of-interest (ROIs), including laminar analyses in seven neocortical regions. In a transgenic mouse model of AD and controls, we compared CO in 56 ROIs, providing information about both regional and network activity. Results highlight cellular and laminar vulnerabilities in AD and illustrate homologies between AD cases and a murine model of AD, with age-related reductions in CO activity within circuits implicated in spatial and discriminative learning. Quantitative CO histochemistry is a useful tool for the ex vivo assessment of functional changes within brain regions and neural networks, and its application has provided support for the hypothesis that mitochondrial dysfunction is involved in the pathophysiology of AD. (The J Histotechnol 30:235, 2007)Submitted September 11, 2007; accepted with modifications October 17, 2007