K. Chandrasekaran et al., EVIDENCE FOR PHYSIOLOGICAL DOWN-REGULATION OF BRAIN OXIDATIVE-PHOSPHORYLATION IN ALZHEIMERS-DISEASE, Experimental neurology, 142(1), 1996, pp. 80-88
In vivo imaging of patients with Alzheimer's disease using positron em
ission tomography (PET) demonstrates progressive reductions in brain g
lucose metabolism and blood flow in relation to dementia severity, mor
e so in association than primary cortical regions, These reductions li
kely follow regional synaptic loss or dysfunction and reflect physiolo
gical down-regulation of gene expression for glucose delivery, oxidati
ve phosphorylation (OXPHOS), and energy consumption in brain, Indeed,
the pattern of down-regulation of expression for both mitochondrial an
d nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer
brain resembles the pattern of down-regulation in normal brain caused
by chronic sensory deprivation. In both cases, do cvn-regulation like
ly is mediated by changes in transcriptional and posttranscriptional r
egulatory factors, Physiological down-regulation of OXPHOS gene expres
sion in Alzheimer's is consistent with PET evidence that cognitive or
psychophysical activation of mildly to moderately demented Alzheimer's
patients can augment brain-blood flow and glucose metabolism to the s
ame extent as in control subjects, If the primary neuronal defect that
leads to reduced brain energy demand in Alzheimer's disease could be
prevented or treated, brain glucose transport and OXPHOS enzyme activi
ties might recover to normal levels. (C) 1996 Academic Press, Inc.