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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

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

Stowe Ann M AM Ireland Sara J SJ Ortega Sterling B SB Chen Ding D Huebinger Ryan M RM Tarumi Takashi T Harris Thomas S TS Cullum C Munro CM Rosenberg Roger R Monson Nancy L NL Zhang Rong R

Journal of neuroinflammation 20170727 1

<h4>Background</h4>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.<h4>Methods</h4>Cerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitiv ...[more]

PMID: 28750671

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Project description:Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and ?-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.To determine the synergistic effects of ?-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.We measured ?-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment.On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase ?-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.

Dataset Information

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

Publications

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

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