Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease

Krish Chandrasekaran, Kimmo Hatanpää, Daniel R. Brady, Stanley I. Rapoport

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

In vivo imaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain. Indeed, the pattern of down-regulation of expression for both mitochondrial and 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, down-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors. Physiological down-regulation of OXPHOS gene expression 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 same 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 activities might recover to normal levels.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalExperimental Neurology
Volume142
Issue number1
DOIs
StatePublished - Nov 1996

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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