Antimicrobial peptides and proteins in Alzheimer's and Parkinson's diseases: implications for biomarker exploration

Biomarkers are necessary tools to validate the diagnosis of Alzheimer's and Parkinson's diseases (AD and PD), especially when clinical symptoms are less apparent in the early stages of diseases. Current biomarkers used in clinical practice rely on brain imaging and cerebrospinal fluid (CSF) levels of amyloid-β (Aβ) peptides and α-synuclein (α-syn) for AD and PD, respectively. However, these diagnostic techniques are not only highly invasive and costly, but they also face limitations in diagnostic accuracy, particularly for preclinical or early stages of diseases. Thus, alternative biomarkers have been sought, preferably those in more accessible and convenient biofluids. Given that antimicrobial peptides and proteins (AMPs) may interact with the neuropathogenesis of AD and PD, AMPs have been recognized as promising candidate biomarkers for AD and PD. Therefore, this review examines the literature on how levels of certain AMPs (lactoferrin, hepcidin, defensin, dermcidin, histatin, cathelicidin L-37, prion protein, amylin or islet amyloid polypeptide, substance P or neurokinin-1, and neuropeptide Y) change in the CSF and more accessible biofluids (serum, plasma, tear, or saliva) in AD and PD patients compared to controls. Based on these findings, this review highlights the advantages, challenges, and future directions of AMP-based biomarkers for AD and PD.