Objective We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre‐dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro‐inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. Methods We applied [11C] Pittsburgh compound B (PiB)‐positron emission tomography to 36 cognitively normal older individuals, and Aβ deposition was quantified by cortical binding potential (PiB‐BPND). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB‐BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. Results Subjects with high PiB‐BPND showed significantly higher percentage of cytotoxic T cells (%CD3+). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB‐BPND. Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB‐BPND and vice versa. Conclusions Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aβ neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.