somewhat less accessible; e.g., muscle) by numerous independent labs around the world, including us. Our finding of a significant decrease in the function of CO in platelet mitochondria isolated from subjects with MCI solidified the hypothesis that interference with mitochondrial function is an early and detectable systemic event in AD pathophysiology which can be leveraged as a biomarker of the disease. While the mitochondrial assays used in that earlier work have shown themselves to be relatively laborious and variable, each requiring mitochondrial isolation from the target cells as a first step, our early work with this technology has revealed a new methodology for the application of reliable tissue histochemistry to cells in suspension, thus enabling the accurate assessment of mitochondrial enzyme activity without confounding mitochondrial isolation, greatly improving sensitivity and ease-of-use, and reducing cost.