Frontiers in Aging Neuroscience · Nov 5, 2026
Association of Plasma TRAIL with Aging and Its Diagnostic Potential in Alzheimer's Disease
By Yali Xu, Yujie Liu, 玲 王 et al.
Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been implicated in the pathogenesis of Alzheimer’s disease (AD). This study aimed to investigate plasma TRAIL levels in patients with AD, patients with amnestic mild cognitive impairment (aMCI), and cognitively unimpaired (CU) individuals. Methods: A total of 396 participants, including 78 patients with AD, 70 patients with aMCI, 70 CU controls, as well as a cohort of 178 cognitively unimpaired (CU) subjects of different ages, were enrolled across a wide age range. Plasma TRAIL levels were measured using an enzyme-linked immunosorbent assay. Correlations among plasma TRAIL and apolipoprotein E (APOE) genotypes were evaluated. Receiver operating characteristic (ROC) curve analyses were used to evaluate the diagnostic performance of plasma biomarkers and to identify the optimal sensitivity and specificity. Results: In the CU cohort, plasma TRAIL levels increased with age (r = 0.579, P < 0.001), showing a significant positive correlation with aging, with no sexrelated differences observed (P = 0.903). Plasma TRAIL levels were significantly elevated in AD patients compared to both aMCI patients (P < 0.001) and CU controls (P < 0.001). No significant difference was found between aMCI and CU groups (P = 0.724). Plasma TRAIL levels were not associated with APOE genotype. Conclusions: Plasma TRAIL levels increase with age and are further significantly elevated in patients with AD, even when compared to age-comparable controls aged ≥ 80 years. This supports its potential as an age- and disease-associated biomarker.