Monomeric C-reactive protein-a key molecule driving development of Alzheimer’s disease associated with brain ischaemia?

Abstract

Alzheimer’s disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with microvasculature, neurons and AD-plaques, Aβ, also, being able to dissociate native-CRP into inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels. Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions. mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic angiogenesis in mouse matrigel implants. mCRP induced tau244–372 aggregation and assembly in vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aβ plaques, tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core regions matched reduced expression of Aβ/Tau. mCRP may be responsible for promoting dementia after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia.

Melatonin induces mechanisms of brain resilience against neurodegeneration

“…This study assessed the beneficial effects of melatonin treatment on cognition and brain status in NoTg and 3xTg‐AD mice. 3xTg‐AD mice presented impairment of recognition memory evaluated by the NOR test as previously reported . Observations also indicated deterioration in exploratory behavior and increase in anxiety‐like conduct, comprising the BPSD‐like phenotype characteristic of 3xTg‐AD strain .…”

Expression of monomeric c-reactive protein in infarcted brain tissue from patients with alzheimerÂ’s disease

“…Mouse monoclonal antibody to human mcrP sub-unit (M8c10) was obtained from dr L.a, and was stated as previously (2). Mouse monoclonal antibodies to p-tau and β-amyloid were purchased from abcam (UK).…”

Dysregulation of Autophagy, Mitophagy, and Apoptosis Genes in the CA3 Region of the Hippocampus in the Ischemic Model of Alzheimer’s Disease in the Rat

“…Age is a major non-modifiable risk factor for brain ischemia and AD [29][30][31][32]. The incidence of cerebral ischemia and AD increases significantly with age in both men and women, covering almost the same number of cases occurring in persons over 65 years of age [29].…”

“…The incidence of cerebral ischemia and AD increases significantly with age in both men and women, covering almost the same number of cases occurring in persons over 65 years of age [29]. Although the entire older population is at risk of ischemic stroke and AD, there are significant gender differences in the occurrence of brain ischemia and AD [29,32]. In general, the incidence of ischemic stroke is higher in men than in women, but at the same age, the number of cases of AD is higher in women than in men [29].…”