Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption

O’Connell, Grant C.; Treadway, Madison B.; Petrone, Ashley B.; Tennant, Connie S.; Lucke-Wold, Noelle; Chantler, Paul D.; Barr, Taura L.

Additionally, our findings suggest that AKAP7 may be a clinically useful biomarker. Early identification of patients at heightened risk for post-stroke BBB disruption allows for clinicians to make more informed decisions regarding the administration of thrombolytic therapies, and can ultimately improve clinical management 6 . As a result, several prior studies have looked to identify blood biomarkers which are predicative for the development of post-stroke BBB disruption. The most widely investigated and once considered the most promising of these potential biomarkers is S100 calcium binding protein B (S100B). Multiple studies have observed early elevated plasma levels of S100B in AIS patients who later develop BBB disruption 37, 38 , however S100B has only exhibited modest levels of diagnostic robustness; in the largest clinical study performed to date evaluating the ability of S100B to identify patients at risk for post-stroke BBB disruption, S100B was only able to do so with 93% sensitivity and 48% specificity 38 . In the study reported here, albeit in a limited sample size, early transcriptional levels of AKAP7 exhibited an ability to predict post-stroke BBB disruption with levels of diagnostic performance exceeding those reported with regards to a majority of previously proposed biomarkers; these findings make AKAP7 a candidate for further clinical evaluation with regards to biomarker use. In addition to providing insight into the role of leukocyte AKAP7 in the context of stroke, this study generated novel data regarding the genomic regulation of AKAP7. This study was the first to provide substantial evidence that all six AKAP7 splice variants which were bioinformatically predicted by the NCBI eukaryotic genome pipeline are expressed in nature. Of these variants, AKAP7x3 and AKAP7x6 are predicted to undergo non-sense mediated decay based on the presence of stop codons more than 50 nucleotides upstream of the first 3′ exon-exon Figure 6 . Expression of AKAP7 splice variants in primary leukocyte populations isolated from peripheral blood. (A-H) Transcriptional expression levels of AKAP7 splice variants in primary leukocyte populations isolated from the peripheral blood of two male and one female heathy donors as measured by qRT-PCR. Splice variants which are translated to produce PKA-binding AKAP7 isoforms are highlighted. Expression levels are presented as fold difference relative to the population of lowest expression and were statistically compared using one-way ANOVA.