Bias-generating factors in biofluid amyloid-β measurements for Alzheimer’s disease diagnosis

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide, yet the dearth of readily accessible diagnostic biomarkers is a substantial hindrance towards progressing to effective preventive and therapeutic approaches. Due to a long delay between cerebral amyloid-β (Aβ) accumulation and the onset of cognitive impairments, biomarkers that reflect Aβ pathology and enable routine screening for disease progression are of urgent need for application in the clinical diagnosis of AD. According to accumulating evidences, cerebrospinal fluid (CSF) and plasma offer windows to the brain as they allow monitoring of biochemical changes in the brain. Considering the high availability and accuracy in depicting Aβ deposition in the brain, Aβ levels in CSF and plasma are regarded as promising fluid biomarkers for the diagnosis of AD patients at an early stage. However, clinical data with intra- and interindividual variations in the concentrations of CSF and plasma Aβ implicate the need to reevaluate current Aβ detection methods and establish a standardized operating procedure. Therefore, this review introduces three bias-generating factors in biofluid Aβ measurement that may hamper the accurate Aβ quantification and how such complications can be overcome for the widespread implementation of fluid Aβ detection in clinical practice.