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

Background: Inflammation promotes amyloidogenesis in animals and markers of inflammation are associated with beta-amyloid (A beta) in humans. Hence, we sought to examine the cross-sectional associations between chronically elevated plasma C reactive protein (CRP) and cortical A beta 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 [F-18] 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 A beta (B-coefficient: - 0.054, SE: 0.026, p = 0.040) and this association seemed to be specific to apolipoprotein E (Apo E) epsilon 4 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 A beta 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 A beta pathology particularly in ApoE epsilon 4 carriers. Investigating the temporal relationships between cerebral A beta and a panel of inflammatory markers would provide further evidence as to whether chronic inflammation might modulate amyloidogenesis in vivo.