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 generally too late to be curable. Therefore, an early diagnosis is extremely important for the intervention. Type 2 diabetes mellitus (T2DM) is also an age-associated disorder, and the patients with T2DM show a significantly increased risk to suffer from Alzheimer's disease. Therefore, searching for biomarkers that can diagnose or 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, prof. Jian-Zhi Wang's team in 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 T2DM, and 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 kind of subjective and dissimilar scores can be received by different doctors even to 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 the large populations while the brain and CSF samples for biochemical analyses are hardly accessible in living patients. The efforts on measurement of plasma Aβ have also shown contradictory results or very marginal differences between Alzheimer's patients and the controls. 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-3β, 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-3β 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 correlation of cognitive impairments with the aforementioned biomarkers, further longitudinal studies are needed to confirm how informative these biomarkers in predicting the conversion of T2DM into Alzheimer's disease".