Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: Superficial laminar cytochrome oxidase associated with disease duration

Among brain regions affected in Alzheimer's disease (AD), the posterior cin gulate shows the earliest and largest decrement in energy metabolism. Posit ron emission tomography (PET) studies have shown that these decrements appe ar before the onset of memory deficits or other symptoms in persons at gene tic risk for AD. This study compares in vivo imaging results and in situ po stmortem analyses by examining the posterior cingulate (area 23) in 15 AD p atients and 13 age-matched nondemented controls using quantitative cytochro me oxidase histochemistry as an intracellular measure of oxidative energy m etabolic capacity. Each of the six layers of the posterior cingulate demons trated a decline in cytochrome oxidase activity in AD relative to controls, whereas adjacent motor cortex showed no significant differences. This decr ement did not appear to be mainly secondary to nonspecific decrement in mit ochondrial enzymes, oxidative stress, cell loss, or histopathology. The cyt ochrome oxidase decrement was most severe in the superficial layer I (-39%) , which demonstrated a correlation to disease duration. Covariance analyses suggest that superficial laminas undergo a functional uncoupling from the deeper layers of posterior cingulate cortex in AD, whereas no such effects are found in motor cortex or controls. These findings expand on previous re sults from PET studies by illuminating the layer-specific cytochrome oxidas e contributions to energy hypometabolism. The findings suggest a decrement of cytochrome oxidase in posterior cingulate cortex, with progressive reduc tion within the superficial laminas linked to disease duration. Such decrem ent could contribute to some of the behavioral symptoms displayed by AD pat ients. This decrement appeared greater in women.