Aβ-reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment.

Area of Science:

• Neuroimmunology
• Neurodegenerative Diseases
• Biomarker Discovery

Background:

• Alzheimer's disease (AD) is characterized by neuroinflammation and amyloid plaques, but the immune system's role in neurodegeneration is not fully understood.
• Investigating the immune response to amyloid may reveal new insights into AD pathogenesis and potential diagnostic tools.

Purpose of the Study:

• To investigate amyloid-reactive T cell levels in individuals with mild cognitive impairment (MCI).
• To evaluate the potential of amyloid-reactive T cell responses as a biomarker for MCI.

Main Methods:

• A polyfunctionality assay was developed to measure five T cell functions in response to diverse amyloid peptide formulations.
• Amyloid-reactive T cell responses were compared between MCI patients and control subjects in two Taiwanese cohorts (EMCIT and TPMIC).

Main Results:

• MCI individuals in both cohorts exhibited significantly higher amyloid-reactive T cell responses compared to controls.
• Amyloid-reactive T cell responses demonstrated superior accuracy in discriminating MCI compared to plasma phosphorylated tau181 (p-tau181).
• Elevated CD4+ and CD8+ T cell responses were observed in MCI patients.

Conclusions:

• Amyloid-reactive T cell polyfunctional responses can be detected in peripheral blood.
• These responses effectively distinguish MCI from normal aging and may serve as a novel biomarker for MCI.
• Further research is warranted to explore the predictive role of these responses in disease progression and their therapeutic potential.