Extravascular CD3+ T Cells in Brains of Alzheimer Disease Patients Correlate with Tau but Not with Amyloid Pathology: An Immunohistochemical Study. and adaptive immune cell subsets to sedentary lifestyle before intervention. We found that PA-induced immunomodulation of CD4+ and CD8+ T cells in CSF correlated with changes in A burden in brain regions associated with executive function. Furthermore, after PA, cognitive scores MEN1 on assessments of memory, processing speed, attention, verbal fluency, and executive function were associated with increased percent representation of circulating na?ve B cells and CD8+ T cells. We review the literature on aMCI-related cognition and immune changes as they relate to exercise, and spotlight how our preliminary data suggest a complex interplay between the adaptive immune system, physical activity, cognition, and A burden in aMCI. at p<0.05 for all assessments and trending values were defined as p0.06. Kruskal-Wallis assessments were performed to compare immune populations between baseline, AET, and ST cohorts. Mann-Whitney assessments were performed to compare the baseline and the overall PA sample (composed of both AET and ST groups) and to compare age, education level, CDR, and cognitive results between groups as appropriate. Fishers Exact assessments were performed to see if sex or race differed between groups. Linear regressions were performed to examine the associations between adaptive immune populations, brain A burden, and cognitive domains. Multiple comparison correction was not performed for this exploratory study and all statistical analyses were performed using GraphPad Prism (La Jolla, CA). RESULTS Physical activity does not modulate frequency of B and T cells in aMCI patients To determine if PA impacted adaptive immunity in the periphery and/or central nervous system (CNS), we analyzed B and T cell subsets in the blood and CSF isolated from a subset of aMCI patients at baseline (n=19) and subsets of aMCI patients after either AET (n=8) or ST (n=9) intervention. Overall, CD19B cells and CD3T cells in the CSF (data not graphed) and blood (Fig. 1ACB) did not differ between interventions. Furthermore, there was no difference in any circulating B or T cell subset, including na?ve B cells, memory B cells, CD4T cells, and CD8T cells (Fig. 1CCD). Given no observable differences in the distribution of B and T cells in the blood and CSF, AET and ST cohorts were pooled. After PA, B and T cells (and their respective subsets) did not differ from baseline in either CSF or blood (Fig. 2). Our preliminary data Tezampanel from this pilot sample of aMCI participants suggests that the distribution of adaptive immune cells in the CSF and blood do not change after an extended period of PA. Open in a separate window Physique 1. Aerobic exercise training and stretching/toning exert minimal effects on adaptive immune cell populations in aMCI patients.General (A) B cell (CD19+) and (B) T cell (CD3+) populations in the blood do not differ between sedentary baseline (squares; n=19) and individuals in the stretching/toning (ST; circles; n=9) and aerobic exercise training (AET; triangles; n=8) interventions. There is also no difference for circulating (C) B cell subsets (baseline, n=19; ST, n=9; AET, n=8) and (D) T cell subsets in the blood. 3 individuals were excluded from overall T cell and T cell subset quantification due to insufficient CD3+ staining. Open in a separate window Physique 2. Physical activity does not alter adaptive immune profiles in aMCI patients.General T cell (CD3+) and B cell (CD19+) populations in (A) blood or (B) cerebrospinal fluid (CSF) do not differ between sedentary baseline (squares) and Tezampanel physical activity (PA) groups, including individuals Tezampanel in the stretching/toning (closed circles) and aerobic exercise training (open circles) interventions. There is also no difference for B cell subsets in the (C) blood and (D) CSF, as well as T cell subsets in the (E) blood and (F) CSF.. B cells were associated with hippocampal A burden To understand the relationship between adaptive immunity and A burden, we first examined whether PA altered A burden in multiple regions of the brain. In aMCI patients, we identified a significant increase in mean cortical A burden (p<0.05) and A deposition in the hippocampus (p<0.05) and precuneus (p<0.05) post-PA (Fig. 3). There was also a trending increase in A burden in Tezampanel the posterior cingulate (p=0.05; Fig. 3E). Next, we sought to determine if there were correlations between A burden and overall B cell populations in the CSF.