Urinary Biomarkers for Neurodegenerative Diseases

Abstract

Global incidence of neurodegenerative diseases (NDDs) such as Alzheimer' s disease (AD) and Parkinson' s disease (PD) is rapidly increasing, but the diagnosis of these diseases at their early stage is challenging. Therefore, the availability of reproducible and reliable biomarkers to diagnose such diseases is more critical than ever. In addition, biomarkers could be used not only to diagnose diseases but also to monitor the development of disease therapeutics. Urine is an excellent biofluid that can be utilized as a source of biomarker to diagnose not only several renal diseases but also other diseases because of its abundance in invasive sampling. However, urine was conventionally regarded as inappropriate as a source of biomarker for neurodegenerative diseases because it is anatomically distant from the central nervous system (CNS), a major pathologic site of NDD, in comparison to other biofluids such as cerebrospinal fluid (CSF) and plasma. However, recent studies have suggested that urine could be utilized as a source of NDD biomarker if an appropriate marker is predetermined by metabolomic and proteomic approaches in urine and other samples. In this review, we summarize such studies related to NDD.

Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease

“…Reliable, noninvasive methods for diagnosing early-stage AD is crucial for increasing the efficiency of available therapeutic treatments. 19 To address this need, we screened for urinary exosomal miRNAs in a well-characterized mouse model of AD, in the early stage, and identified 48 differentially expressed miRNAs (18 upregulated and 30 downregulated). Importantly, miR-34a-5p, which contributes to the pathological development of AD and is supported as a preclinical biomarker of AD, 20,21 was upregulated in our model.…”

“…Reliable, noninvasive methods for diagnosing early‐stage AD is crucial for increasing the efficiency of available therapeutic treatments. 19 …”

Targeting for Success: Demonstrating Proof-of-Concept with Mechanistic Early Phase Clinical Pharmacology Studies for Disease-Modification in Neurodegenerative Disorders

“…Moreover, both these proteins are expressed to an even higher degree in neutrophils, making neutrophils potentially the best source for demonstrating mechanistic proof-of-concept of LRRK2-inhibitors [189]. Another easily accessible biofluid that can be a source for biomarker analysis is urine [190], but also more challenging matrices, such as stool samples, ocular fluids, and mucosal secretions can be considered for biomarker analyses [191]. The challenge of accurate analysis, however, is much higher in such matrices and therefore feasibility of sampling as well as analyte extraction should be considered and demonstrated prior to implementation in clinical trials [191].…”

Distance-based β-amyloid protein detection on PADs for the scanning and subsequent follow-up of Alzheimer's disease in human urine samples

“…19 One report stated that the Aβ protein concentration in urine samples can be effectively determined faster than that in other biological fluidic samples. 20 Correspondingly, Takata et al presented the determination of an Aβ protein concentration in human urine samples based on a western blotting principle with an anti-Aβ antibody, which resulted in high sensitivity, with a detection limit of 40.0 pg mL −1 . 21 However, their method required a large sample consumption, i.e., 10.0 mL, and the sample preparation process included sedimentation before analysis.…”