EVIDENCE FOR PHYSIOLOGICAL DOWN-REGULATION OF BRAIN OXIDATIVE-PHOSPHORYLATION IN ALZHEIMERS-DISEASE

Citation
K. Chandrasekaran et al., EVIDENCE FOR PHYSIOLOGICAL DOWN-REGULATION OF BRAIN OXIDATIVE-PHOSPHORYLATION IN ALZHEIMERS-DISEASE, Experimental neurology, 142(1), 1996, pp. 80-88
Citations number
103
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00144886
Volume
142
Issue
1
Year of publication
1996
Pages
80 - 88
Database
ISI
SICI code
0014-4886(1996)142:1<80:EFPDOB>2.0.ZU;2-J
Abstract
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.