超高感度ELISAによる末梢血リン酸化タウ蛋白バイオマーカー

抄録

Accurate and sensitive molecular biomarkers are needed urgently to make an objective diagnosis of Alzheimer's disease (AD). There is still a substantial unmet need for less invasive and lower–cost blood–based biomarkers to detect brain AD pathology. In this context, we have developed a novel ultrasensitive immunoassay using an ultrasensitive digital array technology (Simoa system, Quanterix) to quantify plasma tau phosphorylated at threonine 181 (p–tau181) in 2017.

In the first cohort composed of 20 AD patients and 15 age–matched controls, the plasma levels of p–tau181 were significantly higher in the AD patients than those in the controls. In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age–matched controls, the plasma concentrations of p–tau181 were significantly higher in the DS group. All of the DS individuals showing an extremely high concentration of plasma p–tau181 (>1.0pg/ml) were older than the age of 40. In the third cohort composed of 11 patients including those with AD and disease controls, the levels of plasma p–tau181 significantly correlated with those of CSF p–tau181.

We have reported for the first time quantitative data on the plasma levels of p–tau181 in controls and patients with AD and DS, and these data suggest that the plasma p–tau181 is a promising blood biomarker for brain AD pathology. Large–scale and well–controlled studies to validate the usefulness of plasma p–tau as a blood biomarker for AD are urgently needed to realize blood–based biomarkers for the diagnosis and evaluation of disease severity of AD in clinical practice.