A new peptide biomarker that could be used for early detection of Alzheimer’s disease has been identified. This peptide could also be used as a tool to enhance delivery of therapeutics. The study findings were published today in Nature Communications.
The cyclic peptide identified, CDAGRKQKC (DAG), was shown to bind to connective tissue growth factor (CTGF), an abundant protein in AD brains in humans and mouse models that is present before the formation of amyloid plaques. The study also showed that DAG homes to diseased or injured brains of mice demonstrating its ability to potentially facilitate the delivery of therapeutics and imaging agents to targeted brain regions.
DAG peptide was identified in AD mouse models of varying ages through in vivo phage display and was shown to target activated astrocytes through immunofluorescence tissue staining of mouse AD brain sections. The team also demonstrated that DAG recognizes AD in human brains through multiple methods, an important finding for future treatments of neurological diseases.
Several experiments in the study demonstrated that CTGF, also known as CCN2, is the DAG receptor. DAG-conjugated silver particles were shown to bind specifically to astrocytoma cells (U251 cells) over non-targeted particles and the presence of CTGF in the U251 cell lysates was identified by mass spectrometry. More evidence was found when CTGF expression was noted to be significantly higher in AD transgenic mouse brains over wild type brains. DAG was also found to home in on brain regions where CTGF was abundant.
"As our research progresses we also foresee CTGF as a potential therapeutic target that is unrelated to amyloid beta (Aβ), the toxic protein that creates brain plaques," Erkki Ruoslahti, M.D., Ph.D., distinguished professor at SBP and senior author of the paper. "Given the number of failed clinical studies that have sought to treat AD patients by targeting Aβ, it's clear that treatments will need to be given earlier--before amyloid plaques appear--or have to target entirely different pathways.”