Increased pro‐inflammatory plasma markers are associated with a longitudinal decrease in left hippocampal volumes in MCI patients

Abstract

AbstractBackgroundApart from amyloid and tau, neuroinflammation plays a significant role in the Alzheimer’s disease (AD) pathogenesis. However, the role of blood bound pro‐inflammatory cytokines on neurodegeneration is still being debated. It is theorised that the activation of inflammation‐associated microglia in the CNS can oscillate through AD’s course, showing elevations in the early stages of AD progression [1]. This study aimed to establish the relationship between the presence of pro‐inflammatory markers and hippocampal volumes, in individuals with an AD diagnosis, late mild cognitive impairment (LMCI) and a cognitively normal control.Method281 participants were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, left and right hippocampal volume values were calculated from the volumetric MRI at baseline and after 12 months follow up. 34 known pro‐inflammatory plasma biomarkers were measured at baseline and 12 months. Principal component analysis (PCA) was conducted on the pro‐inflammatory cytokine change. The change in each participant’s hippocampal volumes was correlated with the independent component‐1 of pro‐inflammatory cytokine change, in the AD, LMCI and control groups.ResultWe demonstrated a negative correlation between changes in left hippocampal volume and changes in the independent component‐1 for pro‐inflammatory cytokines in the LMCI group (r=‐0.245; p=0.011). No correlation was found in the change in left and right hippocampal volumes and the pro‐inflammatory markers in both the AD group, and in the cognitively normal control group.ConclusionThese results indicate that pro‐inflammatory markers can have a deleterious effect on hippocampal volume in individuals with LMCI – and are strongly linked to atrophy in this region. This suggests that peripheral inflammation could be a driving force of neurodegeneration in the early stages of AD’s trajectory. The lack of correlation in the AD patients may imply that once neuronal damage is triggered, a vicious cycle of neurodegeneration occurs, which is independent of peripheral cytokines. These findings suggest that therapeutics which target the pro‐inflammatory response early in AD’s progression trajectory could prevent AD’s progression.