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Samantha Burnham | Research Statistician17 June 2013

CSIRO MATHEMATICS INFORMATICS AND STATISTICS | PREVENTATIVE HEALTH

AIBL: A blood-based predictor for neocortical Aβ burden

Bioinformatics and Biostatistics | Sam Burnham

Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade, Clifford R Jack Jr, David S Knopman, et al. Lancet Neurol 2010; 9: 119–28

The Hypothesis

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Motivation

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Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study, V.L. Villemagne, S.C. Burnham, et al. Lancet Neurol 2013; 12 (4): 357-67


Cohorts

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Methods

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NAB

Demographics

Blood Measures

=• SUVR• + vs -

• Age• Gender• ...

• Blood 1• Blood 2• ...• Blood 176

Cross Validate

Validate

• Base Model

• Full model

Check Value Added

Random Forest


ResultsModel Markers AIBL Imaged Cohort

Sens% (SD%)

Spec% (SD%)

AUC%(SD%)

M1 Age, APOE Genotype, CXCL-13, IgM-1, IL-17, PPY, VCAM-1, Aβ1-42, CDR sum of boxes

79.6 (1.3)

82.4 (1.2)

87.6 (0.7)

M2 Age, APOE Genotype, CXCL-13, IgM-1, IL-17, PPY, VCAM-

1, Aβ1-42

79.6 (1.6)

79.4 (1.4)

83.9 (1.0)

M3 Age, CXCL-13, IgM-1, IL-17,

PPY, VCAM-1, Aβ1-42

73.2(1.8)

73.3(1.8)

80.8 (1.7)

M4 Age, APOE Genotype, CDR sum of boxes

71.4 (1.1)

71.5 (1.1)

78.3 (0.8)

M5 Age, CDR sum of boxes 69.0 (2.1)

68.9 (2.2)

76.0 (2.0)

M6 Age, APOE Genotype 66.7 (1.6)

66.7 (1.6)

70.2 (1.3)

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A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: results from the AIBL study, S.C. Burnham, N.G. Faux, et al. Mol Psy 2013; doi:10.1038/mp.2013.40


ValidationModel Markers ADNI Imaged

CohortSens

% Spec

% AUC

%

M1 Age, APOE Genotype, CXCL-13, IgM-1, IL-17, PPY, VCAM-1, Aβ1-

42, CDR sum of boxes78.3 76.3 84.7

M2 Age, APOE Genotype, CXCL-13,

IgM-1, IL-17, PPY, VCAM-1, Aβ1-4273.9 74.6 81.7

M3 Age, CXCL-13, IgM-1, IL-17, PPY,

VCAM-1, Aβ1-4268.1 73.6 68.8

M4 Age, APOE Genotype, CDR sum of boxes 72.7 67.9 73.7

M5 Age, CDR sum of boxes 59.1 62.3 64.5M6 Age, APOE Genotype 77.3 62.3 67.8

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Other Support

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Summary

• Early detection is critical

• Likely need multimodal and multistage screening process

• Require cheap and non-invasive medium for widespread screen

• Proof of principal for blood biomarker use

• Composite scores, unlikely to be a single marker

• Validation is imperative

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Acknowledgments

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AIBL is a large collaborative study and a complete list of contributors can be found at www.aibl.csiro.au AIBL is funded in part by a grant from the Science and Industry Endowment Fund. We thank all who took part in the study.

Acknowledgements and thanks to the AIBL study participants and their families

David AmesArti AppannahMary BarnesKevin BarnhamJustin BedoShayne BellinghamLynette BonPierrick BourgeatBelinda BrownRachel BuckleySamantha BurnhamAshley BushGraeme ChandlerPrastishtha ChatterjeeKarren ChenRoger ClarnetteSteven CollinsIan CookeTiffany CowieKay CoxRhona CreeganEmily CuninghamDavid DarbyKarl DeruyckPatricia DesmondHang DingJames DoeckeVincent DoreHarriet DowningBelinda DridanKonsta DuesingDenise El- SheikhKathryn Ellis Michael FaheyMaree FarrowNoel FauxMichael Fenech

Jonathan FosterChristopher FowlerMaxime FrancoisJurgen FrippShaun FrostSam GardenerSimon GibsonDavid GothPetra GrahamVeer Gupta Garry HannanDavid HansenKarra HarringtonRichard HeadAndy HillMaryam HorMalcolm HorneBrenda HucksteppPete HudsonAndrew JonesGareth JonesAdrian KamerYogi KanagasingamMohan KarunanithiLisa KeamNeil KilleenAdam KowalczykDebra KrauseBetty KrivdicRebecca LachovitskiChiou Peng LamFiona LambNicola LautenschlagerSimon LawsWayne LeifertNat LenzoHugo Leroux

Falak LftikharQiao-Xin Li Florence LimYen Ying LimTeresa LinternLinda LockettKathleen LucasJames LuiLance MacaulayMark ManoGeorgia MartinsRalph Martins Paul MaruffColin MastersYumiko MatsumotoSabine MatthaesSimon McBrideRachel McKayAndrew MilnerAlinda MondalClaire MontagueLynette MooreAudrey MuirRachel MulliganTabitha NashJulie NigroStewart NuttallNathan O’CallaghanChristopher O’HalloranGraeme O'KeefeTim O’MearaKevin OngLisa OsborneChaoyi PangBernadette ParkerGlen Patten

Jeremiah PeifferSvetlana PejoskaLisa PennyKeyla PerezKelly PertilePramit PhalKerryn Pike Stephanie Rainey-SmithParnesh RanigaAlan RembachCarolina RestrepoMalcolm RileyBlaine RobertsJo RobertsonMark RodriguesAlicia RooneyChristopher RoweRebecca RumbleTim RyanOlivier SalvadoIan SaundersGreg SavageBrendan SilbertHamid SohrabiJulie SyretteCassandra SzoekeKevin TaddeiTania TaddeiMichelle TeggPhilip ThomasDarshan TrivediBrett TrounsonAlison TuckfieldJose VargheseRobyn VeljanovskiGiuseppe Verdile

Victor Villemagne Irene VolitakisMichael VovosStacey Walker Andrew WattMike WeinbornAndrea WilsonBill WilsonMichael WoodwardOlga YastrubetskayaPaul YatesPing ZhangQing ZhangLuping Zhou

http://www.aibl.csiro.au/

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