title: Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration.
abstract: Among brain regions affected in Alzheimer's disease (AD), the posterior cingulate shows the earliest and largest decrement in energy metabolism. Positron emission tomography (PET) studies have shown that these decrements appear before the onset of memory deficits or other symptoms in persons at genetic risk for AD. This study compares in vivo imaging results and in situ postmortem analyses by examining the posterior cingulate (area 23) in 15 AD patients and 13 age-matched nondemented controls using quantitative cytochrome oxidase histochemistry as an intracellular measure of oxidative energy metabolic capacity. Each of the six layers of the posterior cingulate demonstrated a decline in cytochrome oxidase activity in AD relative to controls, whereas adjacent motor cortex showed no significant differences. This decrement did not appear to be mainly secondary to nonspecific decrement in mitochondrial enzymes, oxidative stress, cell loss, or histopathology. The cytochrome 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 results from PET studies by illuminating the layer-specific cytochrome oxidase contributions to energy hypometabolism. The findings suggest a decrement of cytochrome oxidase in posterior cingulate cortex, with progressive reduction within the superficial laminas linked to disease duration. Such decrement could contribute to some of the behavioral symptoms displayed by AD patients. This decrement appeared greater in women.
authors: Institute for Neuroscience and Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA.
authors: J
authors: J
authors: Valla
authors: J D
authors: JD
authors: Berndt
authors: F
authors: F
authors: Gonzalez-Lima
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D030401:Cytochrome-c Oxidase Deficiency; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV