Enhanced Activities of Blood Thiamine Diphosphatase and Monophosphatase in Alzheimer's Disease

Abstract

Background: Thiamine metabolites and activities of thiamine-dependent enzymes are impaired in Alzheimer's disease (AD).

Objective: To clarify the mechanism for the reduction of thiamine diphosphate (TDP), an active form of thiamine and critical coenzyme of glucose metabolism, in AD.

Methods: Forty-five AD patients clinically diagnosed and 38 age- and gender-matched control subjects without dementia were voluntarily recruited. The contents of blood TDP, thiamine monophosphate (TMP), and thiamine, as well as the activities of thiamine diphosphatase (TDPase), thiamine monophosphatase (TMPase), and thiamine pyrophosphokinase (TPK), were assayed by high performance liquid chromatography.

Results: Blood TDP contents of AD patients were significantly lower than those in control subjects (79.03 ± 23.24 vs. 127.60 ± 22.65 nmol/L, P<0.0001). Activities of TDPase and TMPase were significantly enhanced in AD patients than those in control subjects (TDPase: 1.24 ± 0.08 vs. 1.00 ± 0.04, P < 0.05; TMPase: 1.22 ± 0.04 vs. 1.00 ± 0.06, P < 0.01). TPK activity remained unchanged in AD as compared with that in control (0.93 ± 0.04 vs. 1.00 ± 0.04, P > 0.05). Blood TDP levels correlated negatively with TDPase activities (r = -0.2576, P = 0.0187) and positively with TPK activities (r = 0.2426, P = 0.0271) in all participants.

Conclusion: Enhanced TDPase and TMPase activities may contribute to the reduction of TDP level in AD patients. The results imply that an imbalance of phosphorylation-dephosphorylation related to thiamine and glucose metabolism may be a potential target for AD prevention and therapy.

Fig 1. Comparison of blood TDPase, TMPase and TPK activities between AD patients and control participants.

(A). Blood TDPase activity in AD (n = 45) was significantly enhanced as compared with that in control participants (n = 38, 1.24 ± 0.08 vs. 1.00 ± 0.04, P < 0.05;). (B). TMPase activity was markedly increased in AD patients as compared with that in control participants (1.22 ± 0.04 vs. 1.00 ± 0.06, P < 0.01). (C). There was no significant difference in TPK activity between AD and control subjects (0.93 ± 0.04 vs. 1.00 ± 0.04, P > 0.05).

Fig 2. Correlations between blood TDPase, TMPase, TPK activities and TDP, TMP, thiamine levels.

(A). Blood TDP levels showed a significantly negative correlation with TDPase activities in all participants (n = 83). (B). There was no significant correlation between TDP levels and TMPase activities in all participants. (C). There was a significantly positive correlation between TDP levels and TPK activities in all participants. (D). There was no significant correlation between TMP levels and TDPase activities in all participants. (E). Blood TMP contents significantly correlated with TMPase activities in all participants. (F). Blood TMP levels significantly correlated with TPK activities in all participants. (G). Blood thiamine levels did not correlate with TDPase activities in all participants (H). There was no significant correlation between thiamine levels and TMPase activities in all participants. (I). There was no significant correlation between thiamine levels and TPK activities in all participants.

Fig 3. Effects of fasting plasma glucose levels on blood TDPase, TMPase and TPK activities.

(A). Fasting plasma glucose levels in AD patients had no effects on the activities of TDPase (n = 45). (B). There was no significant correlation between fasting plasma glucose levels and TMPase activities in AD patients. (C). Fasting plasma glucose levels had no effects on TPK activities in AD patients. (D). Fasting plasma glucose levels in control subjects had no effects on the activities of TDPase. (E). There was no significant correlation between fasting plasma glucose levels and TMPase activities in control subjects. (F). Fasting plasma glucose levels had no effect on TPK activities in control subjects.