There is strong evidence that brain ischaemic processes increase the risk of suffering age-related dementia. Stroke may induce the development of vascular dementia, but also of Alzheimer’s disease (AD) which is the leading cause of dementia worldwide. Neuroinflammation derived from ischaemic damage in the vessels and brain paremchima may be the causative of neurodegeneration. We have previously demonstrated that the monomeric C- reactive protein (mCRP) may provide a causative link between stroke-associated inflammation and dementia, as its injection into the hippocampus of wild type mice induced loss of memory within one month period [Slevin et al., 2015; Sci Rep 5:13281]. mCRP is a monomeric protein that comes from the dissociation of the pentraxin C-reactive protein (CRP) that remain chronically within the extracellular matrix of ischaemic tissue after stroke. Here we reproduced the mouse model of dementia by mCRP and extended the period post injection up to 6 months to further characterize the mCRP effects on cognition and general behavior. Mice of the transgenic AD strain 5XFAD were also tested for comparison. Treatment with mCRP induced lack of learning and memory at one, three and six months after bilateral injection into the hippocampus of the mice. We assayed the hippocampus tissue for gene expression and protein levels in a search of changes underlying cognitive loss and neurodegeneration. First results revealed lower activation of signaling pathways related to Arc and Egr1 early genes in mCRP mice but not in 5XFAD mice. Main changes in 5XFAD were related to oxidative stress and gliosis markers. We will pursue the molecular study to discern differential patterns between mCRP and 5XFAD mice. Characterizing the mechanisms of mCRP-induced dementia might contribute to decrease AD incidence in the elderly.

Trabajo presentado en el XI Simposi de Neurobiologia: Future technical advances, organizado por la Socitat Catalana de Biologia, en Barcelona, los días 12 y 13 de noviembre de 2018

EU-COP 2014-2020, CRP-SAD, ID: P_37_674, MySMIS code: 103432, contract: 51/05.09.2016; SAF2016‐77703, MINECO and ERDF; 2017-SGR-106, AGAUR.

Peer reviewed