Chronically raised C-reactive protein is inversely associated with cortical β-amyloid in older adults with subjective memory complaints

Abstract

Background: Inflammation promotes amyloidogenesis in animals and markers of inflammation are associated with β-amyloid (Aβ) in humans. Hence, we sought to examine the cross-sectional associations between chronically elevated plasma C reactive protein (CRP) and cortical Aβ in 259 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial (MAPT).

Methods: Cortical-to-cerebellar standard uptake value ratios were obtained using [¹⁸F] florbetapir positron emission tomography (PET). CRP was measured in plasma using immunoturbidity. Chronically raised CRP was defined as having 2 consecutively high CRP readings (>3 mg/l ≤ 10 mg/l) between study baseline and the 1 year visit (visits were performed at baseline, 6 months, 1 year and then annually). Associations were explored using adjusted multiple linear regression.

Results: Chronically raised CRP was found to be inversely associated with cortical Aβ (B-coefficient: -0.054, SE: 0.026, p = 0.040) and this association seemed to be specific to apolipoprotein E (Apo E) ε4 carriers (B-coefficient: -0.130, SE: 0.058, p = 0.027). CRP as an isolated reading measured closest to PET scan was also inversely associated with cortical Aβ when CRP was treated as a dichotomized variable (high CRP > 3 mg/l ≤ 10 mg/l, B-coefficient: -0.048, SE: 0.023, p = 0.043).

Conclusions: Our preliminary findings suggest that inflammation might be beneficial in the early stages of Alzheimer's disease as the immune systems attempts to combat Aβ pathology particularly in ApoE ε4 carriers. Investigating the temporal relationships between cerebral Aβ and a panel of inflammatory markers would provide further evidence as to whether chronic inflammation might modulate amyloidogenesis in vivo.

Keywords: Alzheimer's disease; Apolipoprotein E; C-reactive protein; Cognition; Inflammation; β-Amyloid.