Plasma biomarker candidates predicting the onset of Alzheimer’s disease

Plasma biomarker candidates predicting the onset of Alzheimer's disease

Noriyuki Kimura

Department of Neurology, Oita University, Faculty of Medicine

The early diagnosis of Alzheimer's disease (AD) and broad screening of subjects at risk for AD are important to develop the disease-modifying drugs. Cerebrospinal fluid (CSF) and neuroimaging biomarkers for AD are useful for early diagnosis, risk assessment, monitoring disease progression, and estimation of therapeutic effect. The levels of Aβ_1-42 and phosphorylated tau in CSF and amyloid positron emission tomography (PET) imaging have been established to identify AD patients in early stage. These biomarkers, however, are not appropriate to the screening of AD in large population because of the invasive nature of lumber puncture and limited availability of PET. On the other hand, peripheral blood samples can be collected simply and repeatedly from large numbers of asymptomatic subjects. Previous studies showed various biomarker candidates related to amyloid metabolism, inflammation, cholesterol metabolism, and oxidative stress. Moreover, several longitudinal or cross-sectional studies suggested that low Aβ_1-42/Aβ_1-40 ratio and high Aβ_1-42 level at baseline were related to increased risk of developing AD. A recent meta-analysis, however, indicated heterogeneity and conflicting results due to the difference in assay method, study design, follow-up time, and analysis method. Therefore, further study is required to establish the usefulness of plasma biomarkers in diagnosis or predicting the onset of AD.

Address correspondence to Dr. Noriyuki Kimura, Department of Neurology, Oita University, Faculty of Medicine (1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan)