Elevated Blood Phosphorylated Tau 181 Levels Predict Cognitive and Functional Decline in Alzheimer’s Disease and Mild Cognitive Impairment
Jong-Ling Fuh1, Wei-Ju Lee2, Yung-Shuan Lin1
1Taipei Veterans General Hosp, 2Taichung Veterans General Hospital
Objective:

To determine the effect of blood phosphorylated tau 181 (pTau181) on the mental decline rate of patients with Alzheimer's disease (AD) and  mild cognitive impairment (MCI)

Background:
The diagnostic potential of blood pTau181 in AD has been evaluated. Nevertheless, it needs to be investigated further in different patient populations to determine its prognostic and monitoring capabilities.
Design/Methods:

At two teaching hospitals in Taiwan, AD and MCI patients were recruited and longitudinally followed up at one-year intervals for four years. Annual follow-up rate was about 80%. At yearly follow-ups, Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were used to assess global cognition and function. Blood samples were collected at baseline in tubes containing EDTA, centrifuged, and stored at -80°C in polypropylene tubes until biochemical analysis was performed. The manufacturer's instructions and standard procedures were followed when measuring plasma pTau181 levels with Quanterix SIMOA kits. Coefficients of variance of duplicate measurements were below 15% in all samples.

Results:

A total of 225 patients were recruited at baseline (AD 186, MCI 39). There was a mean age of 76.3±7.4 years and a mean MMSE score of 20.7±5.3. Both MMSE and Clinical Dementia Rating-Sum of Boxes (CDR-SB) decline rates were calculated using the difference between the baseline score and the last follow-up score. The Pearson correlation analysis revealed significant relationships between pTau181 concentration and MMSE decline rate (rs=0.277, p<0.001) as well as CDR-SB decline rate (rs=0.277, p<0.001). Even after adjusting for age and gender, the results were still significant (MMSE, p=0.008; CDR-SB, p=0.003).

Conclusions:
An association was found between increased pTau181 plasma concentration and faster mental decline in AD and MCI patients during a 4-year follow-up period. 
10.1212/WNL.0000000000205361