Mild cognitive impairment: biological diagnostic markers for early stages of Alzheimer's disease

Abstract

ABSTRACTBackground: With the aging population in Japan, the inevitable increase in the prevalence of Alzheimer's disease (AD) and the difficulty in diagnosing the condition. Reliable early diagnostic biomarkers for early stage of AD are needed.Method: We examined a total 570 CSF samples from a variety of diseases, including AD, other types of dementia and controls to quantitate levels of tau protein phosphorylated at serine 199 by sandwich ELISA. WGA‐binding glycoproteins were measured by western blot analysis.Results: The CSF phosphorylated tau protein levels in the AD group were significantly elevated compared to those in all the other non‐AD groups. CSF phosphorylated tau protein levels in the AD progressed from mild cognitive impairment (MCI) group were significantly elevated compared to those in no progression AD from MCI groups and controls. A comparison of the phosphorylated tau protein: WGA‐glycoprotein fragment A ratio for AD and other tauopathies showed that this ratio has potential for differentiating between AD and other tauopathies, particularly dementia with Lewy bodies.Conclusion: Our data showed that measuring cerebrospinal fluid (CSF) levels of phosphorylated tau protein may be useful as an early diagnostic marker in AD and MCI. Furthermore, the measurement of WGA‐binding glycoprotein in CSF may provide a useful tool for differentiating AD from dementia of Lewy bodies and other tauopathies.