Abstract
Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population.Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve.Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p < 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%].Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.
Highlights
∼50 million people in the world are living with dementia and every 3 s a new case of dementia is diagnosed (Christina, 2018)
After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the cognitive function (CN) group, the plasma t-tau, and neurofilament light chain (NfL) were significantly increased in the Alzheimer’s disease (AD) group (p < 0.01, Bonferroni correction)
The most well-established AD biomarkers are mainly based on the core pathological features, including amyloid β (Aβ) deposition [detected by cerebrospinal fluid (CSF)] Aβ42 levels, amyloid positron emission tomography (PET), neurodegeneration [CSF total tau (t-tau)] and phosphorylated (p)-tau levels, structural MRI, and hypometabolism on fluorodeoxyglucose (FDG)-PET (Desikan et al, 2009; Mattsson et al, 2009; Landau et al, 2012)
Summary
∼50 million people in the world are living with dementia and every 3 s a new case of dementia is diagnosed (Christina, 2018). Alzheimer’s disease (AD) is the most common neurodegenerative dementia in older people and is characterized by progressive cognitive decline and behavioral defects with a complex and heterogeneous pathophysiology. High invasiveness, expensive costs, and limited availability hinder their clinical application. Alzheimer’s disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population
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