Plasma‐free amino acid (PFAA) profile is a potential blood‐based biomarker for detection of mild cognitive impairment (MCI)

Abstract

Background Primary prevention of cognitive decline is important while development of disease modifying drugs for early Alzheimer's Disease (AD) is progressing rapidly. As a screening tool for early detection of cognitive decline, blood‐based biomarkers prior to invasive testing such as cerebral spinal fluid examination and positron emission tomography scanning could be beneficial. In our small‐scale pilot study, plasma‐free amino acid (PFAA) profiles of AD patients and mild cognitive impairment (MCI) due to AD were shown to be significantly different from those of cognitively healthy elderly. In order to examine the clinical significance of PFAAs as a novel biomarker, we started an MCI cohort study that enrolls hundreds of MCI subjects to determine practical biomarkers for MCI screening among generally healthy subjects, and to distinguish stable MCI and AD‐converted MCI. The results of interim baseline analysis regarding MCI screening will be presented here. Method MCI subjects from 6 medical sites in Japan (MCI, n=117) and age‐gender‐matched community dwellers in 3 different cities in Japan (healthy control, n=117) were included in the current analysis. At baseline visit, plasma samples were collected under fasting condition. The concentrations of PFAAs and plasma amines were analyzed with LC/MS or LC/MS/MS and serum biochemistry tests were done. Observation of the clinical status of MCI subjects for 3 years after the blood collection is ongoing. Result Several PFAAs including essential amino acids of MCI subjects were significantly lower than those of healthy control. There were no significant differences in plasma amine concentrations between MCI and control group. In addition, several serum biochemistry parameters including serum albumin of MCI subjects were significantly lower. These differences were independent of age and gender. Conclusion Both PFAAs including essential amino acids and serum biochemistry including albumin were shown to be potential biomarkers for MCI screening. The validation of this results will be conducted in another subset in this MCI cohort study. For further investigation, we will conduct multivariable analysis and create the robust algorithm for MCI screening. Also, observation of the clinical status of MCI subjects will continue to distinguish stable MCI and AD‐converted MCI.