Fuel Homeostasis and the Nervous System

Lukiw, W J, Handley, P, Sutherland, M K, Wong, L, McLachlan, D R, W. J. Lukiw, P. Handley, M. K. Sutherland, L. Wong, D. R. McLachlan

Our laboratory has measured mRNA pool sizes in neocortex afflicted with Alzheimer's disease (AD). We have observed a repression of gene expression in the temporal and parietal regions compared to age-matched control neocortex. These changes in messenger RNA pool size closely parallel the observed alterations in local cerebral metabolic rates for glucose (LCMR-g), as detected by positron emission tomography (PET). For example, deficits in both gene transcription and glucose metabolism appear to be the greatest in AD-affected superior temporal neocortex (Brodmann area 22) but are less apparent in the primary visual cortex (Brodmann area 17) or in the cerebellum. The unresolved question is whether changes in gene expression are the cause or effect of altered glucose metabolism. However, the non-random reductions in the pool size for certain neocortical mRNAs argue in favour of altered gene expression as the primary event.