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

OBJECTIVE: Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer's disease (AD) risk only in apoliprotein E4 genotype ( APOE ε4) allele carriers. The objective of this study was to examine the interactive effects of plasma CRP and apoliprotein E ( APOE ) genotype on cognition and AD biomarkers.

METHODS: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study was analyzed, including APOE genotype; plasma CRP concentrations; diagnostic status (i.e., MCI and dementia due to AD); Mini-Mental State Exam (MMSE) and Clinical Dementia Rating (CDR) Dementia Staging Instrument; cerebral spinal fluid (CSF) concentrations of amyloid-β 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 one, and 70 (12.4%) had two APOE ε 4 alleles. Only among participants who had two APOE ε4 alleles, elevated CRP was associated with lower MMSE at baseline [ β (95%CI): -0.52 ( -1.01, -0.12)] and 12-month follow-up [β (95%CI): -1.09 (-1.88, -0.17)] after adjusting for sex, age and education. The interaction of two APOE ε4 alleles and elevated plasma CRP was associated with increased CSF levels of t-Tau (β = +11.21, SE = 3.37, p < 0.001) and p-Tau (β = +2.74, SE = 1.14, p < 0.01). Among those who had no APOE ε4 allele, elevated CRP was associated with decreased CSF t-Tau and p-Tau. These effects were stronger at 12-month follow-up.

CONCLUSIONS: CRP released during peripheral inflammation could be a mediator in APOE ε4 related AD neurodegeneration and serve as a drug target for AD.