ABSTRACT
BACKGROUND: Exosomes are nano-sized extracellular vesicles secreted by most cell types and abundantly present in body fluids, including blood, saliva, urine, cerebrospinal fluid, and breast milk. Exosomes can spread toxic amyloid-beta (Aß) and hyperphosphorylated tau between cells, contributing to neuronal loss in Alzheimer's disease (AD). OBJECTIVE: To explore changes in the morphology, number, and pathological protein levels of urinary exosomes in AD patients compared with age-matched healthy subjects. METHODS: In this study, enzyme-linked immunosorbent assay was used to detect the levels of Aß1-42 and P-S396-tau (normalized by CD63) in urinary exosomes of AD patients and matched healthy subjects. We used transmission electron microscopy and nanoparticle tracking analysis to observe the exosomes. RESULTS: We found that the levels of Aß1-42 and P-S396-tau in the urinary exosomes of AD patients were higher than those of matched healthy controls. Exosomes taken from AD patients were more numerous. CONCLUSION: The differences in levels of Aß1-42 and P-S396-tau and the quantity of urinary exosomes between AD patients and healthy controls may provide a basis for early diagnosis of AD.
Subject(s)
Alzheimer Disease/urine , Exosomes/metabolism , Aged , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/urine , Biomarkers/urine , Brain/diagnostic imaging , Enzyme-Linked Immunosorbent Assay , Exosomes/ultrastructure , Female , Humans , Male , Microscopy, Electron, Transmission , Peptide Fragments/urine , Pilot Projects , tau Proteins/urineABSTRACT
Alzheimer disease is the most common cause of dementia, yet its clinical diagnosis remains uncertain until an eventual postmortem histopathology examination. Currently, therapy for patients with Alzheimer disease only treats the symptoms; however, it is anticipated that new disease-modifying drugs will soon become available.Diagnostic tools for detecting Alzheimer disease at an incipient stage that can reliably differentiate the disease from other forms of dementia are of key importance for optimal treatment. Biomarkers have the potential to aid in a correct diagnosis, and great progress has been made in the discovery and development of potentially useful biomarkers in recent years. This includes single protein biomarkers in the cerebrospinal fluid, as well as multi-component biomarkers, and biomarkers based on gene expression. Novel biomarkers that use blood and urine, the more easily available clinical samples, are also being discovered and developed. The plethora of potential biomarkers currently being investigated may soon provide biomarkers that fulfill different functions, not only for diagnostic purposes but also for drug development and to follow disease progression.
