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The Journal of Neuroscience, July 1, 2001, 21(13):4923-4930
Energy Hypometabolism in Posterior Cingulate Cortex of
Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase
Associated with Disease Duration
J.
Valla1, 2,
Jason D.
Berndt1, and
F.
Gonzalez-Lima1
1 Institute for Neuroscience and Department of
Psychology, University of Texas at Austin, Austin, Texas 78712, and
2 Harrington Alzheimer's Disease Research Laboratory,
Arizona Alzheimer's Research Center, Phoenix, Arizona 85006
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.
Key words:
cytochrome oxidase; energy metabolism; posterior cingulate cortex; Alzheimer's disease; brain mapping; gender
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134923-08$05.00/0
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