Abstract
Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (−0.37, P < 0.0001), and increased along the Alzheimer’s continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology.
Highlights
Amyloid accumulation, tau deposits and neurodegeneration are the most representative pathological features of Alzheimer’s disease (AD)
We explored whether the relationships between plasma p-tau181 and Positron emission tomography (PET) biomarkers were mediated by cerebrospinal fluid (CSF) biomarkers, including Aβ1-42, total tau (t-tau), and p-tau
PET imaging acquisition and processing Data of brain amyloid PET were acquired by the florbetapir (AV-45) tracer, and the summary data are regularly updated on the website of Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Summary
Tau deposits and neurodegeneration are the most representative pathological features of Alzheimer’s disease (AD). Detection of these pathologies are vital for screening out the target population at risk among people with intact cognition or mild cognitive impairment (MCI). Positron emission tomography (PET) and cerebrospinal fluid (CSF) are considered to be the most effective methods for detecting and tracking pathological changes in the brain. Measurements of CSF biomarkers are difficult to be employed in large-scale screening, because of its invasiveness and the harsh requirement for skilled operators [2]. There is a substantial need for less invasive and lower cost biomarkers in the periphery, which could be used in the clinical routine and community screening. More researchers engage in the discovery of plasma biomarkers to implement the biological definition of AD and to enrich the target population for clinical trials [3, 4]
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