Lin Kooi Ong, PhD

Hilal S, Ikram A, Verbeek MM, Franco OH, Stoops E, Vanderstichele H, et al. C-Reactive Protein, Plasma Amyloid-β Levels, and Their Interaction With Magnetic Resonance Imaging Markers. Stroke. 2018

The Rotterdam Study is a population-based prospective cohort study among middle age and elderly persons living in the Ommoord district in the city of Rotterdam, the Netherlands. In this study, Hilal et al. examined whether the levels of plasma C-reactive protein (CRP), an inflammation marker, are associated with Magnetic Resonance Imaging (MRI) markers such as lacunes, white matter hyperintensities, cerebral microbleeds, perivascular spaces, and atrophy of brain structures in a population of 2814 participants. Hilal and colleagues then measured the levels of plasma amyloid- β (Aβ) isoforms in a subsample of 736 individuals, and examined their interaction with CRP levels and MRI markers. The team observed higher levels of plasma CRP were associated with higher lacunar counts, larger volume of white matter hyperintensities, changes in microbleed counts, enlarged perivascular space and reduced gray matter volume. Further, the team found that effects such as lacunar counts, enlarged perivascular space and microbleed counts were augmented by an interaction between CRP and Aβ levels.

The usage of only one inflammatory marker (CRP, a non-specific marker of inflammation) and the fact that CRP results were not adjusted for various inflammatory conditions may limit the interpretation of the data. It seems reasonable that the inclusion of a comprehensive panel of inflammatory markers could further improve the understanding of the relationship between inflammation processes and MRI markers.

Aβ is a peptide of 36 to 43 amino acids, and it is produced through sequential proteolytic processing of amyloid precursor protein, by β-secretase and γ-secretase. Aβ monomers have the propensity to self-assemble into oligomers that can exist in several forms (such as dimer, an assembly of 2 monomers, trimer, an assembly of 3 monomers and so on). These oligomers eventually continue to aggregate to form into insoluble amyloid fibrils that deposit in the brain to yield dense core plaques. Emerging literature has indicated that Aβ oligomers, rather than the monomers or insoluble fibrils, may be responsible for the cellular pathology. While the authors measured the levels of three specific Aβ isoforms (Aβ1–38, Aβ1–40 and Aβ1–42) using ELISA, further studies to identify the conformational states of plasma Aβ and brain amyloid imaging using positron emission tomography are warranted.

Treatment strategies to target inflammatory processes may represent an attractive avenue to delay progression of neurodegenerative conditions.