Background Resolution is the final stage of the inflammatory response, when restoration of tissue occurs. Failure may lead to chronic neuroinflammation, known as part of pathology in Alzheimer’s disease (AD) brain. Methods Specialized pro-resolving mediators (SPMs), receptors, biosynthetic enzyme, and downstream effectors involved in resolution were analyzed in post mortem hippocampal tissue from AD-patients and non-AD subjects. SPMs were analyzed in cerebrospinal fluid (CSF). Results Presence of SPMs and SPM receptors was demonstrated in the human brain. Levels of the SPM lipoxin A4 (LXA4) were reduced in AD - both in CSF and hippocampus. An enzyme involved in LXA4 synthesis and two SPM receptors were elevated in AD brains. LXA4 and RvD1 levels in CSF correlated to mini-mental state examination (MMSE) scores. Conclusions The resolution pathway exists in the brain and described alterations strongly suggest its dysfunction in AD. Correlations with MMSE suggest a connection with cognitive function in AD.

More than 20 peptides have been identified in neurones of the brain, spinal cord and periphery. In several cases a peptide occurs together with a 'classical' transmitter in the same neurone. This raises new questions about the process of neurotransmission and may have important implications for our understanding and treatment of mental disorders.

No abstract

Inflammation in the brain is a prominent feature in Alzheimer’s disease (AD). Recent studies suggest that chronic inflammation can be a consequence of failure to resolve the inflammation. Resolution of inflammation is mediated by a family of lipid mediators (LMs), and the levels of these specialized pro-resolving mediators (SPMs) are reduced in the hippocampus of those with AD. In the present study we combined analysis of LMs in the entorhinal cortex (ENT) from AD patients with in vitro analysis of their direct effects on neurons and microglia. We probed ENT, an area affected early in AD pathogenesis, by liquid chromatography-tandem mass spectrometry (LC-MS-MS), and found that the levels of the SPMs maresin 1 (MaR1), protectin D1 (PD1) and resolvin (Rv) D5, were lower in ENT of AD patients as compared to age-matched controls, while levels of the pro-inflammatory prostaglandin D2 (PGD2) were higher in AD. In vitro studies showed that lipoxin A4 (LXA4), MaR1, RvD1 and protectin DX (PDX) exerted neuroprotective activity, and that MaR1 and RvD1 down-regulated Aβ42-induced inflammation in human microglia. MaR1 exerted a stimulatory effect on microglial uptake of Aβ42. Our findings give further evidence for a disturbance of the resolution pathway in AD, and indicate that stimulating this pathway is a promising treatment strategy for AD.

No abstract