Monomeric CRP
A KEY MOLECULE DRIVINGDEVELOPMENT OF ALZHEIMER’SDISEASE?

BACKGROUND
C-reactive protein (CRP) is a multipotent protein that
undergoes conformational changes between circulating
native pentameric CRP (pCRP), pentameric symmetricalforms (pCRP*) and monomeric CRP (mCRP) forms. mCRP
exhibits strong pro-inflammatory activity and activates
platelets, leukocytes, and endothelial cells. Abundantdeposition of mCRP in inflamed tissues plays a role in several
disease conditions, such as ischemia/reperfusion injury,
Alzheimer’s disease, and cardiovascular disease.
Conversion of pCRP to mCRP induces inflammatory
signalling, monoacyl phosphatidylcholine generated by PLA2,
or by oxidation lipid acyl chains, promotes binding anddissociation of pCRP to mCRP. mCRP gains functionally active
neoepitopes that carry out highly pro-inflammatory and prothrombotic features, thus mCRP can bind cholesterol and Reference: Rajab, Ibraheem & Hart, Peter & Potempa, L.A.:
enter plasmatic membrane and activate pro-inflammatory How C-Reactive Protein Structural Isoforms With Distinctive
Bioactivities Affect Disease Progression. Frontiers inresponses.
Immunology; 11. 2126 (2020)

Deposition of mCRP, which has a much lower aqueous solubility than pCRP, has been shown in the brain in infarcted
areas of Alzheimer diseases patients and in regions with amyloid burden, in atherosclerotic plaques in vasculardisease and in other foci of inflammatory tissue injuries.
Reference: Garcia-Lara E, Aguirre S, Clotet N, Sawkulycz X, Bartra C, Almenara-Fuentes L, et al. Antibody Protection Against Long-TermMemory Loss Induced by Monomeric C-Reactive Protein in a Kouse Model of Dementia. Biomedicines 9(7):828 (2021)

PRESENCE OF CRP IN THE BRAIN
CRP is primarily produced by the liver in response tomacrophage secreted IL-6. CRP expression, however, may be
upregulated in glutamate neurons during specific diseasestates, such as Alzheimer's dementia. Human and animalstudies show that mCRP co-localizes with α-amyloid plaques
and with phosphorylated-tau protein in hippocampus.
Other studies indicate that CRP is produced in the CNS,
either in neurons, glia, and/or microvessel endothelial cells,
during immune and homeostatic challenges with someindications that CRP may be neurotoxic. Furthermore, CRP
contributes to increasing blood-brain barrier permeability
through the endothelial modifications (e.g. after trauma)
and thus allowing other inflammatory signaling factors toReference: Cipollini V et al.: Emerging Biomarkers in Vascular enter the CNS.
Cognitive Impairment and Dementia: From Pathophysiological
Pathways to Clinical Application. Int J Mol Sci. 8;20(11):2812 (2019)

MONOMERIC CRP AND DEMENTIA
Inflammatory damage spreading from small blood vessels and linked dysregulation of amyloid β metabolism in theneurons have been implicated in the origin of Alzheimer disease. It is known that mCRP accumulates in brain microvessels after ischemic stroke, where it promotes aberrant angiogenesis, accumulation of amyloid β and probably
de novo synthesis of amyloid β. Therefore, mCRP may cause both vascular and neuronal degeneration and underlie
the processes leading to poststroke dementia. Specific targeting of mCRP can be a therapeutic approach in areasin which rapid increases in its local generation are expected, such as stroke-affected brain areas, in order to haltsubsequent neurodegeneration and dementia. The prevalence of dementia in stroke survivors is about 30%, and ahigh proportion of these patients suffer from Alzheimer disease in addition to those with either vascular or mixed
Alzheimer disease together with vascular dementia.
Al-Baradie described mCRP localized in the cerebral tissue of damaged vascular brain regions associated withneuroinflammation and neurodegeneration in an immunohistochemical study. They described co-localization ofmCRP with β-amyloid or p-Tau in IHC samples
from individuals with eurodegenerative disease.
Co-localization of mCRP with β-amyloid (A–C,microvessels, plaques and neurons, respectively)
and co-localization of mCRP with p-Tau inneurons/fibrils (D,E) was shown. Control sample(F) shows a cortical region unaffected (noevidence of neurodegeneration).

Reference: Al-Baradie RS et al.: Monomeric C-Reactive Protein Localized in the
Cerebral Tissue of Damaged Vascular Brain Regions Is Associated With NeuroInflammation and Neurodegeneration-An Immunohistochemical study. Front
Immunol.; 12:644213 (2021)

IMPACT OF CIRCULATING MONOMERIC CRP ON ALZHEIMER DISEASE
Mouse model: Zhang et al. published a study with mice treated with mCRP, and showed that peripheral mCRP
causes cerebrovascular inflammation and damages in ApoE4, but not in ApoE2 or ApoE3, mice via decreasing CD31
and increasing phosphorylated CD31. Garcia-Lara et al. found that anti mCRP antibody was able to completely
block mCRP-induced chronic memory loss in a murine model of dementia where mCRP was injected into
the hippocampus resulting in symptoms of neurodegeneration.
References:Zhang Z et al.: Monomeric C-reactive protein via endothelial CD31 for neurovascular inflammation in an ApoE genotype-dependent pattern: Arisk factor for Alzheimer's disease? Aging Cell; 20(11) (2021)
Garcia-Lara E, Aguirre S, Clotet N, Sawkulycz X, Bartra C, Almenara-Fuentes L, et al. Antibody Protection Against Long-Term Memory Loss
Induced by Monomeric C-Reactive Protein in a Kouse Model of Dementia. Biomedicines 9(7):828 (2021)

Human studies: Need to be performed.

Human Monomeric CRP ELISA

Cat.No. BA1026
Sandwich ELISA: capture MAb specific to mCRP
Size: 96 wells
Measuring range: 1 - 50ng/ml
Sample type: serum
Regulatory status: RUO

Manufactured by BioLab Assays s.r.o.

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