Early ß-amyloid accumulation in the brain is associated with peripheral T cell alterations.

INTRODUCTION: Fast and minimally invasive approaches for early diagnosis of Alzheimer's disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral ß-amyloidosis has raised the question of whether immune markers could be used as proxies for ß-amyloid accumulation in the brain. METHODS: Here, we apply multidimensional mass-cytometry combined with unbiased machine-learning techniques to immunophenotype peripheral blood mononuclear cells from a total of 251 participants in cross-sectional and longitudinal studies. RESULTS: We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain ß-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. DISCUSSION: Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help identify and develop novel diagnostic tools for early AD assessment and better understand clinical outcomes.