Early detection of Alzheimer's disease by peptides from phage display screening

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective treatment so far. As clinical trials show that early-stage patients are more likely to respond to potential interventions, various technologies have been used to search blood biomarkers for the early diagnosis of AD. Phage display could be used to select specific peptides against desired target and here, we established a peptide binding assay based on phage display peptide library to detect early-stage AD patients. We first selected peptides from phage display library against plasmas from AD patients (n = 10) and normal healthy controls (n = 10), respectively, in the discovery set. Then, we further characterized one AD-specific peptide (AD#1 peptide) and one control-specific peptide (Con#1 peptide), and evaluated their diagnostic performance in independent validation set (35 AD patients, 45 MCI, 45 controls and 20 PD patients). Our results show that both AD#1 peptide and Con#1 peptide could distinguish AD/MCI patients from controls and combination of these two peptides could greatly improve the diagnostic performance (AUC is above 0.80 in ROC curve analysis). In addition, we found that AD#1 peptide stained Aβ-treated primary astrocyte and bound to recombinant human YKL-40 protein in in-vitro assay. It supports that AD#1 peptide detects AD inflammation related cytokine. Thus, the detection assay based on phage-derived peptides may offer a novel blood biomarker test for the early diagnosis of AD.

Keywords: Alzheimer’s disease; Biomarker; Early diagnosis; Inflammation; Phage display.