We employed the preferential copper ferrocyanide staining method to investigate neuronal mitochondrial metabolic competence in an animal model of Alzheimer's disease (AD). To that aim, we studied the appearance of signs of mitochondrial dysfunction in triple transgenic mice (3xTg-AD) that express mutant forms of the amyloid precursor protein (APP), presenilin-1 (PS1), and tau protein. The activity of succinic dehydrogenase (SDH) was cytochemically investigated at the level of cristae and inner mitochondrial membranes of mitochondria of hippocampal CA1 pyramidal neurons obtained from 3xTg-AD and control (PS1-Kl) mice at 10 months of age. Employing a computer-assisted image analysis system connected to a transmission electron microscope, we analyzed morphometric parameters of SDH-positive mitochondria such as: 1) numeric density (Nv: number of mitochondria/cubic micron of cytoplasm); 2) average organelle volume (V); 3) volume density (Vv: volume fraction of mitochondria/cubic micron of cytoplasm), and 4) the ratio (R) of the total area of the cytochemical precipitate due to SDH activity divided by the total mitochondrial area. Results from this study indicate that 3xTg-AD mitochondria show a significant decrease of Nv, a significant increase of V, and a not statistically significant reduction of R, while Vv was unchanged. SDH, the complex II of the mitochondrial respiratory chain, is a step in the oxidative phosphorylation process that becomes critical specially when energy demand is high. Thus, given the high metabolic rate of neurons, any impairment in the activity of this system can represent a serious threat for survival. Our findings lend support to the idea that mitochondrial dysfunction is involved in AD and are in line with recent studies indicating that both APP and b-amyloid can localize to mitochondria and produce mitochondrial impairment and oxidative damage.