Abstract

Objective: To investigate the association between plasma amyloid-β (Aβ) levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform.Methods: We prospectively recruited 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid positron emission tomography (PET) scanning, and detailed neuropsychological tests. Patients were classified into a normal control (NC, n = 25) or Alzheimer’s disease (AD, n = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results.Results: The plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid PET positivity by receiver operating characteristic curve analysis [area under the curve of 0.952 (95% confidence interval, 0.892–1.000)]. Although there were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups, higher levels of plasma Aβ42/40 were negatively correlated only with verbal and visual memory performance.Conclusion: Our results demonstrated that plasma Aβ analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline.

Highlights

  • Alzheimer’s disease (AD), a neurodegenerative disease, is the most common cause of cognitive impairment and dementia (Jack et al, 2018)

  • The platform had excellent sensitivity in the Aβ analysis, and the changes upon specific binding of Aβ42 and Aβ40 ranged from approximately 3.241 ± 0.053%−10.684 ± 1.296% and from 1.563 ± 0.169% to 3.919 ± 0.632%, respectively, depending on the concentrations of Aβ in 1 mM phosphate-buffered saline (PBS) (Figure 1B)

  • We investigated the association between plasma Aβ levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform fabricated by combining micro/nanotechnology with DEP

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Summary

Introduction

Alzheimer’s disease (AD), a neurodegenerative disease, is the most common cause of cognitive impairment and dementia (Jack et al, 2018). The pathophysiology of AD is characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau deposition in the brain (Pereira et al, 2021). Growing evidence suggests that Aβ deposition in the brain initiates AD by inducing a chain of events involving the accumulation of toxic tau, which leads to downstream neurodegeneration (Jack et al, 2013, 2014; Pereira et al, 2021). Considering the advantages in terms of cost, reduced invasiveness, and repeated measurement ability, there is a need for the development of blood-based AD biomarkers. Since Aβ is present at extremely low levels in the blood (on the scale of pg/mL) (Risacher et al, 2019), a more accurate measurement method with higher sensitivity and selectivity is required for the development of more precise bloodbased AD biomarkers. With advances in measurement technology, it has become possible to measure various forms of Aβ; published results far appear to be fairly conflicting, and it has been reported that several factors influence the measurement of Aβ in the blood (Wang et al, 2020)

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