A Systematic Review on Urinary Biomarkers for Early Diagnosis of Alzheimer’s Disease (AD)

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that commonly affects the older population whose symptoms are only visible during the later stage which renders the available treatment ineffective. Our study attempts to provide a solution to this problem by identifying urinary biomarkers that could be used in the first-line screening of a larger population for AD before analysing with more sophisticated blood and CSF based biomarkers, which provide high sensitivity on comparison. A systematic review was performed using the keywords “Alzheimer”, “urine”, “biomarkers” and “metabolomics” following the PRISMA criteria, to identify urinary biomarkers for the early diagnosis of Alzheimer’s disease. From the performed study, three metabolites were identified namely 5-hydroxy indole acetic acid, L-arginine and allantoin as biomarkers whose level was altered in AD samples compared to controls. In AD, 5-hydroxy indole acetic acid level was downregulated in urine probably because of the extensive serotonergic denervation that has been observed in the AD brain. Increased levels of L-arginine in the brain which act as a precursor to nitric oxide due to the action of NO synthase might potentially lead to neurotoxicity when present in excess, and is also known to be in synergy with ROS. Increased levels of allantoin in urine is due to the action of increased ROS in the system reacting with uric acid. Here, we provide an overview of all the reported metabolites obtained from the search, by discussing their influence in AD pathology. This study identified three metabolites in urine that could function as potential biomarkers for AD based on significant changes observed between disease and control samples, along with its recurrence and commonality in different models namely mice and human. However, longitudinal and cross-sectional follow-up studies are required for the validation of these biomarkers.