Stimulation of pro-resolving activities in Alzheimer´s disease
Swedish Research Council
Alzheimer's disease & other dementias
Inflammation is present in the brain of patients suffering from neurodegenerative disorders, such as Alzheimer?s disease (AD). A new line of research on inflammation indicates a failure in the progression to the resolution phase of inflammation in disorders with a deleterious inflammatory component. In studies on human brain material and CSF, we have shown that factors related to inflammatory resolution are altered in AD, and that CSF levels of so called specialized pro-resolving mediators (SPMs), are reduced in AD and correlate with cognitive function. The goals for the present project are to elucidate the potential for a novel pathogenic strategy based on modulation of the resolution of inflammation in AD, and to provide information as to the validity of using resolution factors as tools for diagnosis and assessment of treatments. Hypothesis: Stimulation of pro-resolving activities is a potential treatment strategy in AD. Specific aims are i) in vitro studies on mechanisms of resolution in neurons and glia, ii) test in cell cultures and animal models if stimulation of pro-resolving pathways lead to an amelioration of parameters considered pathological with regard to AD, and iii) analysis of clinical materials (CSF, blood and post mortem brain tissue), in order to determine the potential of resolution as diagnostic biomarker, and to further characterize the state of resolution and inflammation in the AD brain.