Abstract
Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer disease (AD) risk only in APOE ε4 allele carriers; the objective of this study was to examine the interactive effects of plasma CRP and APOE genotype on cognition and AD biomarkers. Data from the Alzheimer's 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. Among 566 ADNI participants, 274 (48.4%) had no, 222 (39.2%) had 1, and 70 (12.4%) had 2 APOE ε4 alleles. Among only participants who had 2 APOE ε4 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 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 alleles, elevated CRP was associated with decreased CSF t-Tau and p-Tau. These effects were stronger at the 12-month follow-up. CRP released during peripheral inflammation could be a mediator in APOE ε4-related AD neurodegeneration and serve as a drug target for AD.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.