Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer's disease.
Clinical data suggest that high-dose thiamine (vitamin B1) may have a mild beneficial effect in some patients with Alzheimer's disease (AD). Since this action could be related to a brain thiamine deficiency, we measured directly levels of free (nonphosphorylated) thiamine and its phosphate esters, thiamine monophosphate and thiamine diphosphate (TDP), and activities of three TDP-metabolizing enzymes (thiamine pyrophosphokinase, thiamine diphosphatase, and thiamine triphosphatase) in autopsied cerebral cortex of 18 patients with AD and 20 matched controls. In the AD group, mean levels of free thiamine and its monophosphate ester were normal, whereas levels of TDP were significantly reduced by 18 to 21% in all three cortical brain areas examined. Activities of the TDP-metabolizing enzymes were normal in the AD group, suggesting that decreased TDP is not due to altered levels of these enzymes. The TDP decrease could be explained by a cerebral cortical deficiency in AD of ATP, which is needed for TDP synthesis. Although the magnitude of the TDP reduction is slight, a chronic subclinical TDP deficiency could contribute to impaired brain function in AD and might provide the basis for the modest improvement by thiamine in cognitive status of some patients with AD.
Mastrogiacoma
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F
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Canada.
Bettendorff
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L
Grisar
T
T
Kish
S J
SJ
D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D001344:Autopsy; D001923:Brain Chemistry / Q000502:physiology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D013836:Thiamin Pyrophosphokinase / Q000378:metabolism; D013837:Thiamin-Triphosphatase / Q000378:metabolism; D013831:Thiamine / Q000378:metabolism*; D013833:Thiamine Monophosphate / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000378:metabolism; D013838:Thiamine Triphosphate / Q000378:metabolism; D013997:Time Factors
D013838:Thiamine Triphosphate; D013833:Thiamine Monophosphate; D007655:Ketoglutarate Dehydrogenase Complex; D013836:Thiamin Pyrophosphokinase; D017766:Acid Anhydride Hydrolases; D013837:Thiamin-Triphosphatase; C023837:nucleoside-diphosphatase; D013835:Thiamine Pyrophosphate; D013831:Thiamine