Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease.
OBJECTIVE
To investigate the levels of glutathione transferase (GST), a protective enzyme against aldehydes, and especially 4-hydroxynonenal (HNE) in the brain and ventricular CSF of autopsied AD and normal control subjects.


BACKGROUND
Studies have implicated increased levels of oxidative stress in the brain in the pathogenesis of AD. Decreased levels of polyunsaturated fatty acids and increased levels of markers of lipid peroxidation have been reported in the brain in AD, particularly in areas severely affected in the disease. HNE, one marker of lipid peroxidation, is neurotoxic in neuronal culture and in vivo and is elevated in AD brain and CSF.


METHODS
We measured levels of GST activity and protein in multiple brain regions and ventricular CSF in short-postmortem-interval AD patients and age-matched prospectively evaluated control subjects.


RESULTS
A decrease in GST activity in all brain areas was observed in AD compared with controls with significant decreases in the amygdala, hippocampus and parahippocampal gyrus, inferior parietal lobule, and nucleus basalis of Meynert. Levels of GST protein also were depleted in most brain regions in AD. A significant decrease in GST activity and protein levels was also found in ventricular CSF in AD.


CONCLUSIONS
Reduced levels of GST, a protective mechanism against HNE, may have a role in the pathogenesis of neuron degeneration in AD.
Lovell
M A
MA
Department of Chemistry, Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
Xie
C
C
Markesbery
W R
WR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology; D000679:Amygdala / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002552:Cerebral Ventricles / Q000201:enzymology*; D002555:Cerebrospinal Fluid / Q000201:enzymology*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D013377:Substantia Innominata / Q000378:metabolism
D005982:Glutathione Transferase