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Novel Biomarkers to Identify Conversion of Type 2 Diabetes Mellitus into Alzheimer’s Disease

Novel Biomarkers to Identify Conversion of Type 2 Diabetes Mellitus into Alzheimer’s Disease


Alzheimer’s disease is the most common cause of senile dementia, and the prevalence is increasing with population aging. When the clinical diagnosis of Alzheimer’s disease is made, it is too late to be curable. Therefore, an early diagnosis is extremely important for intervention. Type 2 diabetes mellitus (T2DM) is also an age-associated disorder, and  patients with T2DM show a significantly increased risk to suffer  Alzheimer’s disease. Therefore, searching for biomarkers that can predict conversion of T2DM into Alzheimer’s disease makes it possible to start an early intervention, and eventually reduces the incidence of Alzheimer’s disease.

In a paper published online in the journal of EBioMedicine (please see at http://www.sciencedirect.com/science/article/pii/S2352396416300457, or at doi:10.1016/j.ebiom.2016.02.014), prof. Jian-Zhi Wang’s team at Huazhong University of Science and Technology reported that alterations of several circulating molecules, olfactory function and age are correlated with a mild cognitive impairment in patients with type 2 diabetes mellitus (T2DM), and the combination of these different factors can improve the diagnostic accuracy. These findings shed light on the early prediction among the T2DM population who will develop Alzheimer’s disease and thus enable early intervention to this currently incurable neurodegenerative disorder.

Prof. Jian-Zhi Wang says that the current clinical diagnosis of Alzheimer’s disease has been made by using different cognitive tests, but these measures are subjective and dissimilar scores can be received by different doctors even with the same patient. Recent studies have validated that brain amyloidosis and neurodegeneration can serve as biomarkers of Alzheimer’s disease. However, measuring these biomarkers need positron emission tomography (PET), magnetic resonance imaging (MRI), or cerebrospinal fluid (CSF), which are not affordable by many while brain and CSF samples for biochemical analyses are appropriate for living patients. Efforts for measurement of plasma Aβ have also shown contradictory results. Therefore, there is an urgent need for developing objective, noninvasive, affordable and readily-accessible biomarkers/methods for the early diagnosis of Alzheimer’s disease.

Through a four and half years multicenter, retrospective, nested case-control study, prof. Jian-Zhi Wang’s team discovered that activation of the peripheral circulating GSK-3b, expression of ApoE ε4, dysfunction of the olfactory function, and aging are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these factors can significantly improve the diagnostic accuracy. They also developed a simple protocol for measuring the total and the inactivated form of GSK-3b in human platelets. As the method is simple and easy to operate with low cost and good repeatability, it is suitable for application in clinical laboratories.

Prof. Jian-Zhi Wang is very excited with this translational research, nonetheless, she also points out the limitation or the further direction of the current study: “although we have designed training set and validation set respectively to assure the biomarkers in diagnosing cognitive impairments, further longitudinal studies are needed to confirm how informative these biomarkers in predicting the conversion of T2DM into Alzheimer’s disease”.