Amyloid beta-specific T cell response is enhanced in individuals with mild cognitive impairment

Abstract

Abstract Background: Neuroinflammation and deposition of amyloid plaques are key features of patients with Alzheimer’s dementia or mild cognitive impairment (MCI), but little is known about the role of amyloid-reactive immune response in cognitive decline. Using an amyloid b-specific T cell polyfunctionality assay, we tested samples from the Epidemiology of Mild Cognitive Impairment in Taiwan study (EMCIT) and the Taiwan Precision Medicine Initiative of Cognitive Impairment and dementia (TPMIC) study. Results: Both cohorts showed enhanced amyloid-reactive T-cell responses in individuals with MCI. In the EMCIT cohort, the individual’s amyloid peptide pool-reactive CD4+ and CD8+ total response frequencies were significantly larger in MCI patients (n=69; CD4+: 0.79%; CD8+: 0.67%) than in control individuals (n=69; CD4+: 0.27%; CD8: 0.4%; both p < 0.05). Notably, CD4+ T cell total response discriminated MCI versus control (AUROC, 0.72) with significantly higher accuracy than p-Tau181 (AUROC: 0.59, p < 0.01). In the TPMIC cohort, both amyloid peptide pool-reactive CD4+ and CD8+ total response frequencies were also higher in MCI individuals (n=41; CD4: 1.3%, CD8: 1.91%) than in control (n=79, CD4: 0.15%, CD8: 0.28%; both p < 0.001). Amyloid peptide pool-reactive total CD4+ and CD8+ T cell response frequencies outperformed p-Tau181 in their discriminative accuracy of MCI (CD4+ AUROC, 0.97; CD8+ AUROC, 0.96; p-Tau181 AUROC, 0.72; both p < 0.001). Other amyloid peptide formulations similarly induced an increase of T cell response in MCI individuals and demonstrated superior discriminative accuracy than p-Tau181. Conclusion: Our study indicates that T cell-specific, amyloid-associated T cell response increases in individuals with MCI. T cell response against amyloid is a novel biomarker of mild cognitive impairment. Further studies are needed to investigate the potential role of amyloid-T cell response as a risk factor for future cognitive decline.