CSF tau protein phosphorylated at threonine 231 as a potential biomarker of early-stage Alzheimer's disease

Abstract

Mild cognitive impairment (MCI), a syndrome characterized by cognitive impairment without dementia, which primarily affects the episodic memory is often considered as an initial stage of Alzheimer's disease (AD). Tau protein phosphorylated at threonine 231 (pT231) has recently been proposed as a possible biological marker of early AD. This study as part of the project “Detection and tracking of biological markers for early therapeutic intervention in sporadic Alzheimer's disease” observed whether the measurement of pT231 in cerebrospinal fluid (CSF) correlates with the pathological process of neurofibrillary degeneration characteristic for AD. A positive answer to this question would mean that this marker could be used for early detection of AD. Concentration of pT231 was determined using ELISA method in CSF of 34 patients with probable AD, 25 MCI patients and 7 healthy controls. Levels of pTau231 were significantly higher in the group of AD patients than in MCI patients or healthy control. Levels of pTau231 did not differ significantly between AD and MCI group. ROC curve analysis showed that pTau231 could differentiate AD patients from healthy control with sensitivity of 73.5% and specificity of 85.7%. Cut-off level for pTau231 (1.904 U/ml) was defined when the sum of specificity and sensitivity was maximized. 32% MCI patients had pTau231 levels higher than cut- off, while the rest of MCI patients (68%) had normal pT231 levels. Group of 32% MCI patients should be defined as the risk group with amnestic MCI. However, follow-up period of minimum 5 years is necessary to determine if patients from risk group will actually convert to AD. In conclusion, pT231 could be useful biological marker for AD detection in the preclinical stage of the disease.