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P3‐105: CORRELATION OF NOVEL PROTEOMIC ANALYTES WITH ALZHEIMER'S DISEASE BIOMARKERS IN CEREBROSPINAL FLUID FROM MILD SPORADIC ALZHEIMER'S DISEASE DEMENTIA PATIENTS

2014; Wiley; Volume: 10; Issue: 4S_Part_18 Linguagem: Inglês

10.1016/j.jalz.2014.05.1194

1552-5279

Sun Ah Park, Yung‐Keun Kwon, Hyeong Jun Kim, Tae Eun Kim, Yoon‐Jeong Kim, Jong Hun Kim, Sang Won Seo, Duk L. Na, Jeong Yeon Kim, Seong Hye Choi,

Dementia and Cognitive Impairment Research

The concentrations and combined ratios of beta amyloid 1-42 (A β42) and tau proteins are widely used as Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). However,due to large variability in measurements and poor prediction of clinical courses, further applications of these biomarkers are limited. We conducted this study to develop novel biomarkers that supplement the shortage of known AD biomarkers. High throughout proteomic analysis was performed in mild sporadic AD patients who demonstrated a high degree of certainty of AD pathology according to revised AD criteria. The expression of individual proteins was quantitated using a l abel-free protein quantification method, and these were competed with the concentrations of A β42, pTau181, and tTau. The MMSE score in AD patients was 21.3 ± 4.9, and the average CDR scores were 0.8 ± 0.3. All of the CSF samples were sufficient to establish the diagnostic cut-off value of the Aβ42/pTau181 and Aβ42/tTau ratios in our laboratory.Fifteen of the 724 protein samples demonstrated a significant correlation with at least one of the AD biomarkers (p < 0.05). Seven of these proteins were previously identified as AD biomarkers, whereas eight were newly found. T he direction of change in the levels of Aβ42 was found to be opposite to those of the levels of the Tau proteins in all analytes. Regarding the Aβ42 levels, four proteins revealed a significant correlation. Another four proteins demonstrated a significant correlation with both pTau181 and tTau concentrations. We found three proteins to have a significant relationship only with pTau181, whereas two proteins showed a significant correlation only with tTau levels. Interestingly, t here were no analytes that demonstrated a correlation with both Aβ42 and Tau proteins simultaneously. The remaining proteins showed a distinct correlation with the combined ratio of Aβ42/ pTau181 or Aβ42/tTau; however, the relationship with the individual concentrations was statistically negligible. Through our work, we identified new candidate CSF biomarkers of AD. Considering their biological roles, these candidate markers are suggested to be intimately related to AD pathophysiology. Further investigations are needed to identify their values as surrogate biomarkers or therapeutic targets in AD.