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Arch Neurol. 2012 Oct;69(10):1318-25.

Blood-based protein biomarkers for diagnosis of Alzheimer disease.

Collaborators (396)

Weiner M, Aisen P, Petersen R, Jack CR Jr, Jagust W, Trojanowki JQ, Toga AW, Beckett L, Green RC, Saykin AJ, Morris J, Liu E, Montine T, Gamst A, Thomas RG, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe RA, Foster N, Reiman EM, Chen K, Mathis C, Morris J, Cairns NJ, Taylor-Reinwald L, Shaw L, Lee VM, Korecka M, Crawford K, Neu S, Foroud TM, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder PJ, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider LS, Pawluczyk S, Spann BM, Brewer J, Vanderswag H, Heidebrink JL, Lord JL, Johnson K, Doody RS, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Ances B, Carroll M, Leon S, Mintun MA, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah RC, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon MJ, Glodzik L, De Santi S, Doraiswamy PM, Petrella JR, Coleman RE, Arnold SE, Karlawish JH, Wolk D, Smith CD, Jicha G, Hardy P, Lopez OL, Oakley M, Simpson DM, Porsteinsson AP, Goldstein BS, Martin K, Makino KM, Ismail MS, Brand C, Mulnard RA, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Swerdlow RH, Apostolova L, Lu PH, Bartzokis G, Silverman DH, Graff-Radford NR, Parfitt F, Johnson H, Farlow MR, Hake AM, Matthews BR, Herring S, van Dyck CH, Carson RE, MacAvoy MG, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung GY, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam MM, Lipowski K, Wu CK, Johnson N, Sadowsky C, Martinez W, Villena T, Turner RS, Johnson K, Reynolds B, Sperling RA, Johnson KA, Marshall G, Frey M, Yesavage J, Taylor JL, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson AE, Norbash A, Johnson PL, Obisesan TO, Wolday S, Bwayo SK, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee TY, Bartha R, Johnson S, Asthana S, Carlsson CM, Potkin SG, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre DW, Kataki M, Zimmerman EA, Celmins D, Brown AD, Pearlson GD, Blank K, Anderson K, Santulli RB, Schwartz ES, Sink KM, Williamson JD, Garg P, Watkins F, Ott BR, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen HJ, Miller BL, Mintzer J, Longmire CF, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D, Ames D, Ellis K, Macaulay L, Martins R, Masters C, Milner A, O'Meara T, Rowe C, Szoeke C, Appannah A, Barnes M, Barnham K, Bedo J, Bellingham S, Bon L, Bourgeat P, Brown B, Buckley R, Burnham S, Bush A, Chandler G, Chatterjee P, Chen K, Clarnette R, Collins S, Cowie T, Cox K, Creegan R, Cuningham E, Cyarto E, Darby D, Deruyck K, Desmond P, Ding H, Doecke J, Dore V, Downing H, Dridan B, Duesing K, Fahey M, Farrow M, Faux N, Fenech M, Fowler C, Francois M, Fripp J, Frost S, Gardener S, Gibson S, Goth D, Graham P, Gupta V, Hannan G, Hansen D, Harrington K, Head R, Hill A, Hor M, Horne M, Huckstepp B, Jones A, Jones G, Kamer A, Kanagasingam Y, Karunanithi M, Keam L, Kowalczyk A, Krause D, Krivdic B, Lachovitzki R, Lam CP, Lamb F, Lautenschlager N, Laws S, Leifert W, Lenzo N, Leroux H, Lftikhar F, Li QX, Lim F, Lim YY, Lintern T, Lockett L, Lucas K, Mano M, Marczak C, Martins G, Maruff P, Matsumoto Y, Matthaes S, McBride S, McKay R, Mondal A, Mulligan R, Nash T, Nigro J, Nuttall S, O'Callaghan N, O'Keefe G, Ong K, Osborne L, Pang C, Parker B, Patten G, Peiffer J, Pejoska S, Penny L, Perez K, Pertile K, Phal P, Rainey Smith S, Raniga P, Rembach A, Restrepo C, Riley M, Roberts B, Robertson J, Rodrigues M, Rooney A, Rumble R, Ryan T, Salvado O, Samuel M, Saunders I, Savage G, Silbert B, Sohrabi H, Syrette J, Taddei K, Taddei T, Tegg M, Thomas P, Trivedi D, Trounson B, Tuckfield A, Varghese J, Veljanovski R, Verdile G, Villemagne V, Volitakis I, Vovos M, Vrantsidis F, Walker S, Watt A, Weinborn M, Wilson A, Wilson B, Woodward M, Yastrubetskaya O, Yates P, Zhang P, Zhang Q.

Author information

  • 1The Australian E-Health Research Centre, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

Abstract

OBJECTIVE:

To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD).

DESIGN:

Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data.

SETTING:

General community-based, prospective, longitudinal study of aging.

PARTICIPANTS:

A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort.

RESULTS:

A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve.

CONCLUSIONS:

This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.

Comment in

PMID:
22801742
[PubMed - indexed for MEDLINE]
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