Single cell analysis of the peripheral immune landscape in Alzheimer reveals a distinct adaptive immune signature

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the most frequent cause of dementia. Recent evidence suggests involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.MethodWe comprehensively mapped systemic immune changes in AD patients from the Amsterdam Dementia Cohort with mild cognitive impairment (MCI; n = 21; 65y±6; 52% female) or dementia (n = 59; 63y±8; 53% female) compared to controls (n = 35; age 61y±6; 46% female), using high‐dimensional single‐cell characterization.ResultWe found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory re‐expressing CD45RA (TEMRA) cells in the MCI stage of AD. This subset formed unique, dynamic networks with subsets of CD4+ T cells. In addition, several innate and adaptive immune subsets correlated to cerebrospinal fluid (CSF) levels of amyloid‐β and phosphorylated tau, and measures for cognitive decline. Specifically, subsets of memory B cells were negatively associated with CSF biomarker levels of neurodegeneration and neuroinflammation in AD patients.ConclusionTogether, these findings highlight substantial adaptive immune changes in AD and signify the demand for a greater understanding of how these cells contribute to underlying brain pathology.