Impact of C-Reactive Protein on Cognition and Alzheimer Disease Biomarkers in Homozygous Apolipoprotein E ɛ4 Carriers.

Background and Objectives Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer disease (AD) risk only in APOE e4 allele carriers; the objective of this study was to examine the interactive effects of plasma CRP and APOE genotype on cognition and AD biomarkers. Methods Data from the Alzheimer9s Disease Neuroimaging Initiative (ADNI) study were analyzed, including APOE genotype; plasma CRP concentrations; diagnostic status (i.e., mild cognitive impairment and dementia due to AD); Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Dementia Staging Instrument scores; CSF concentrations of β-amyloid peptide (Aβ42), total tau (t-Tau) and phosphorylated tau (p-Tau); and amyloid (AV45) PET imaging. Multivariable regression analyses tested the associations between plasma CRP and APOE on cognitive and biomarker outcomes. Results Among 566 ADNI participants, 274 (48.4%) had no, 222 (39.2%) had 1, and 70 (12.4%) had 2 APOE e4 alleles. Among only participants who had 2 APOE e4 alleles, elevated CRP was associated with lower MMSE score at baseline (β [95% confidence interval] −0.52 [−1.01, −0.12]) and 12-month follow-up (β −1.09 [−1.88, −0.17]) after adjustment for sex, age, and education. The interaction of 2 APOE e4 alleles and elevated plasma CRP was associated with increased CSF levels of t-Tau (β = 11.21, SE 3.37, p Discussion CRP released during peripheral inflammation could be a mediator in APOE e4–related AD neurodegeneration and serve as a drug target for AD.