Qiushan Tao1,2, Ting Fang Alvin Ang2,3,4, Samia C Akhter-Khan5,6, Indira Swetha Itchapurapu1, Ronald Killiany3, Xiaoling Zhang7, Andrew E Budson8,9,10, Katherine W Turk8,9,10, Lee Goldstein9, Jesse Mez8,9, Michael L Alosco8,9, Wei Qiao Qiu11,9,12. 1. Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, USA. 2. Framingham Heart Study, Boston University School of Medicine, Boston, USA. 3. Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, USA. 4. Slone Epidemiology Center, Boston University School of Medicine, Boston, USA. 5. Department of Psychology, Humboldt University of Berlin, Berlin, Germany. 6. Department of Health Service & Population Research, King's College London, London, UK. 7. Department of Medicine, Boston University School of Medicine, Boston, USA. 8. Department of Neurology, Boston University School of Medicine, Boston, USA. 9. Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, USA. 10. Veterans Affairs Boston Healthcare System, Boston, USA. 11. Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, USA wqiu67@bu.edu. 12. Department of Psychiatry, Boston University School of Medicine, Boston, USA.
Abstract
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 ε4 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.
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 ε4 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.
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