Impact of C-Reactive Protein on Cognition and Alzheimer Disease Biomarkers in Homozygous APOE [Latin Small Letter Open E]4 Carriers. (21st September 2021)

• Record Type: Journal Article
• Authors: Tao, Qiushan; Alvin Ang, Ting Fang; Akhter-Khan, Samia C.; Itchapurapu, Indira Swetha; Killiany, Ronald; Zhang, Xiaoling; Budson, Andrew E.; Turk, Katherine W.; Goldstein, Lee; Mez, Jesse; Alosco, Michael L.; Qiu, Wei Qiao
• Is Part Of: Neurology. Volume 97:Number 12(2021)
• Publication Date: 2021-09-21
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000012512
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : 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 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. Methods: 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. Results: Among 566 ADNI participants, 274 (48.4%) had no, 222 (39.2%) had 1, and 70 (12.4%) had 2 APOE ε 4 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. Discussion: CRP released during peripheral inflammation could be a mediator in APOE ε4–related AD neurodegeneration and serve as a drug target for AD.