Cleaved Annexin A1 is elevated in neurodegenerative dementia and is associated with pathological burden of amyloid and inflammatory cytokines

Abstract

AbstractBackgroundInflammation is usually terminated by resolution, mediated by pro‐resolving mediators including Annexin A1 (AnxA1) which is known to be involved in granulocyte trafficking as well as efferocytosis of apoptotic neutrophils. Failure in resolution may lead to chronic inflammation, which has been considered a pathological hallmark of neurodegenerative diseases. We investigated the expression levels of AnxA1 in post‐mortem brain tissues and their correlation with pathological burden in dementia.MethodProtein levels of AnxA1 were measured in post‐mortem parietal cortices (Brodmann area BA40) as well as frontal cortices (BA9) of well characterized Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), Alzheimer’s disease (AD) patients and healthy controls via immunoblotting. Amyloid and cytokines were quantified via ELISA and Luminex respectively.ResultIn BA40, expression of cleaved (33 kDa) AnxA1 was found to be elevated in DLB and AD as compared to controls. While cleaved AnxA1 (33 kDa) showed an increasing trend in BA9, the increase was not significant. In our cohort of patients with dementia, levels of cleaved AnxA1 was also positively correlated with ratio of soluble amyloid‐β42/40. In addition, as AnxA1 activation has been shown to increase production of anti‐inflammatory markers such as IL10 and IL13. We measured IL10 and IL13 and found positive correlations with AnxA1.ConclusionOur results suggest that elevation of AnxA1 in DLB and AD may be a compensatory response to the increased inflammation in neurodegenerative diseases, in an attempt to resolve inflammation. Previous in vitro and in vivo research also revealed elevated AnxA1 in 5XFAD mice models and in vitro AnxA1 treatment reduced pro‐inflammatory and increased anti‐inflammatory cytokines. Our results demonstrate that similar associations are observed in post‐mortem samples and suggest that AnxA1 may play a similar role in humans.