Adaptive lymphocyte profiles correlate to brain A? burden in patients with mild cognitive impairment.

ABSTRACT: We previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment.Cerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66?±?6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)?, and quantification of cytokine and immunoglobin levels. Amyloid (A)? deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels.Soluble A?42 in the cerebrospinal fluid declined as A? deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as A? deposition in the posterior cingulate cortex increased. In contrast, increased A? burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APO?4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with A? deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden.Elevations in brain A? burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during A? accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, A? dysregulation during memory decline on a larger cohort collected at multiple centers.AETMCI NCT01146717.

SUBMITTER: Stowe AM 

PROVIDER: S-EPMC5530920 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature