Cortical glutaminase, beta-glucuronidase and glucose utilization in Alzheimer's disease.
Large pyramidal neurons of rat and human neocortex stain immunohistochemically for phosphate-activated glutaminase (PAG). In a limited number of postmortem brains, we find large reductions in cortical PAG activity in Alzheimer's disease (AD). This finding is consistent with histological evidence that pyramidal neurons are affected in AD. The reductions are greater than those found in the same samples in choline acetyltransferase (ChAT) but the possible deleterious effects of coma and similar premortem factors on human PAG activity have yet to be assessed. The activity of beta-glucuronidase, a lysosomal enzyme which occurs in reactive astrocytes, is elevated in the same samples. Positron emission tomography (PET) studies, using 18F-fluorodeoxyglucose (FDG), have demonstrated significant deficiencies in glucose metabolism in the cortex in AD, with the parietal, temporal and some frontal areas being particularly affected. We found in serial scans of 13 AD cases, including one relatively young (44-46 year old) familial case, an exacerbation of the defect over time in most cases. We have found a negative correlation between the regional metabolic rates for glucose (LCMR(s] measured premortem and the beta-glucuronidase activities measured postmortem on a few AD cases that have come to autopsy. The correlations between LCMR(s) and PAG and ChAT activities tend to be positive. The results are consistent with previous suggestions that decreased LCMR(s) in AD reflect local neuronal loss and gliosis.
McGeer
E G
EG
Kinamen Laboratory of Neurological Research, Dept. of Psychiatry, University of B.C., Vancouver, Canada.
McGeer
P L
PL
Akiyama
H
H
Harrop
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D014055:Tomography, Emission-Computed
D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005966:Glucuronidase; D005972:Glutaminase; D005947:Glucose