Measurement of Blood Thiamine Metabolites for Alzheimer's Disease Diagnosis

Abstract

BackgroundBrain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD).AimsTo explore the diagnostic value of the measurement of blood thiamine metabolites for AD.MethodsBlood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable γ that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients.ResultsTDP and the γ exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The γ had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the γ can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for γ) and frontotemporal dementia (84.6% for TDP, 100.0% for γ).Interpretation.The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits.

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer’s Disease

“…Both the TDP level and the activity of TDP-dependent enzymes are significantly reduced in blood and brain autopsy samples from AD patients [7][8][9]. Our previous study showed that TDP reduction is a significant biomarker for AD diagnosis [10]. The reduction of brain glucose metabolism and its possible pathogenic indicator, TDP reduction, implicate multiple pathogenic pathways in AD, including oxidative stress [11], neuroinflammation [12], and enhanced activity of glycogen synthase kinase-3 [13] and b-secretase [14].…”

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

“…Both TDP level[8,9,10,11] and activities of TDP-dependent enzymes[12,13,14,15] have been demonstrated to be significantly decreased in AD. Previous studies have demonstrated that thiamine deficiency can induce or aggravate AD-like pathologies, such as neuritic plaques, and hyperphosphorylation of tau, finally memory deficits[16].…”

Vitamin B1 in critically ill patients: needs and challenges

“…However, there is evidence of age-related differences [15]. The elderly (>76 years of age) are known to have a reduced total thiamine compound concentration that can be 21%-26% lower than that of the middle aged [57,137]. A longitudinal study of over 300 participants spanning 3 years by Wilkinson et al [15] examined a younger, healthy population (mean age 41.5 years) of 100 volunteers and compared it to an elderly population (mean age 76 years) of 221 participants.…”

“…Its involvement in these metabolic pathways and its intracellular abundance has made TPP a popular analyte for assessing thiamine status. However, there are also proposed non-cofactor roles of thiamine compounds within the immune system, gene regulation, oxidative stress response, cholinergic activity, chloride channels and neurotransmission [8,[56][57][58][59][60][61].…”