Research Article| Volume 333, ISSUE 1-2, P9-12, October 15, 2013

Association of plasma C-reactive protein levels with the diagnosis of Alzheimer's disease

Published:August 26, 2013DOI:


      C-reactive protein (CRP) participates in the systemic response to inflammation. Previous studies report inconsistent findings regarding the relationship between plasma CRP and Alzheimer's disease (AD). We measured plasma CRP in 203 subjects with AD, 58 subjects with mild cognitive impairment (MCI) and 117 normal aging subjects and administered annual Mini-Mental State Examinations (MMSE) during a 3-year follow-up period to investigate CRP's relationship with diagnosis and progression of cognitive decline. Adjusted for age, sex, and education, subjects with AD had significantly lower levels of plasma CRP than subjects with MCI and normal aging. However, there was no significant association between plasma CRP at baseline and subsequent cognitive decline as assessed by longitudinal changes in MMSE score. Our results support previous reports of reduced levels of plasma CRP in AD and indicate its potential utility as a biomarker for the diagnosis of AD.


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        • Akiyama H.
        • Barger S.
        • Barnum S.
        • Bradt B.
        • Bauer J.
        • Cole G.M.
        • et al.
        Inflammation and Alzheimer's disease.
        in: Neurobiology of Aging. 21(3). Elsevier, 2000: 383-421
        • Engelhart M.J.
        • Geerlings M.I.
        • Meijer J.
        • Kiliaan A.
        • Ruitenberg A.
        • Van Swieten J.C.
        • et al.
        Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study.
        Arch Neurol. May 2004; 61: 668-672
        • Black S.
        • Kushner I.
        • Samols D.
        C-reactive Protein.
        J Biol Chem. Nov 19 2004; 279: 48487-48490
        • Völkel D.
        • Zimmermann K.
        • Zerr I.
        • Lindner T.
        • Bodemer M.
        • Poser S.
        • et al.
        C-reactive protein and IL-6: new marker proteins for the diagnosis of CJD in plasma?.
        Transfusion. Dec 2001; 41: 1509-1514
        • Kravitz M.S.
        • Pitashny M.
        • Shoenfeld Y.
        Protective molecules–C-reactive protein (CRP), serum amyloid P (SAP), pentraxin3 (PTX3), mannose-binding lectin (MBL), and apolipoprotein A1 (Apo A1), and their autoantibodies: prevalence and clinical significance in autoimmunity.
        J Clin Immunol. Nov 2005; 25: 582-591
        • Iwamoto N.
        • Nishiyama E.
        • Ohwada J.
        • Arai H.
        Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections.
        Neurosci Lett. Aug 15 1994; 177: 23-26
        • Schmidt R.
        • Schmidt H.
        • Curb J.D.
        • Masaki K.
        • White L.R.
        • Launer L.J.
        Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study.
        Ann Neurol. Aug 2002; 52: 168-174
        • Nilsson K.
        • Gustafson L.
        • Hultberg B.
        C-reactive protein: vascular risk marker in elderly patients with mental illness.
        Dement Geriatr Cogn Disord. Jan 2008; 26: 251-256
        • Nilsson K.
        • Gustafson L.
        • Hultberg B.
        C-reactive protein level is decreased in patients with Alzheimer's disease and related to cognitive function and survival time.
        Clin Biochem. Oct 2011; 44: 1205-1208
        • O'Bryant S.E.
        • Waring S.C.
        • Hobson V.
        • Hall J.R.
        • Moore C.B.
        • Bottiglieri T.
        • et al.
        Decreased C-reactive protein levels in Alzheimer disease.
        J Geriatr Psychiatry Neurol. Mar 2010; 23: 49-53
        • Licastro F.
        • Pedrini S.
        • Caputo L.
        • Annoni G.
        • Davis L.J.
        • Ferri C.
        • et al.
        Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?.
        J Neuroimmunol. Feb 2000; 103: 97-102
        • Hu W.T.
        • Holtzman D.M.
        • Fagan A.M.
        • Shaw L.M.
        • Perrin R.
        • Arnold S.E.
        • et al.
        Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease.
        Neurology. Aug 28 2012; 79: 897-905
        • McKhann G.
        • Drachman D.
        • Folstein M.
        • Katzman R.
        • Price D.
        • Stadlan E.M.
        Clinical diagnosis of Alzheimer´s disease: Report of the NINCDS-ADRDA Work group under the auspices of department of health and human services task force on Alzheimer´s diesease.
        Neurology. 1984; 34: 939-944
        • Laird N.M.
        • Ware J.H.
        Random-effects Models for Longitudinal Data.
        Biometrics. 1982; 38: 963-974
        • März W.
        • Scharnagl H.
        • Hoffmann M.M.
        • Boehm B.O.
        • Winkelmann B.R.
        The apolipoprotein E polymorphism is associated with circulating C-reactive protein (the Ludwigshafen risk and cardiovascular health study).
        Eur Heart J. Dec 2004; 25: 2109-2119
        • Bennett D.A.
        • Schneider J.A.
        • Wilson R.S.
        • Bienias J.L.
        • Berry-Kravis E.
        • Arnold S.E.
        Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people.
        J Neurol Neurosurg Psychiatry. Sep 2005; 76: 1194-1199