title: A blood gene expression marker of early Alzheimer's disease.
abstract: A marker of Alzheimer's disease (AD) that can accurately diagnose disease at the earliest stage would significantly support efforts to develop treatments for early intervention. We have sought to determine the sensitivity and specificity of peripheral blood gene expression as a diagnostic marker of AD using data generated on HT-12v3 BeadChips. We first developed an AD diagnostic classifier in a training cohort of 78 AD and 78 control blood samples and then tested its performance in a validation group of 26 AD and 26 control and 118 mild cognitive impairment (MCI) subjects who were likely to have an AD-endpoint. A 48 gene classifier achieved an accuracy of 75% in the AD and control validation group. Comparisons were made with a classifier developed using structural MRI measures, where both measures were available in the same individuals. In AD and control subjects, the gene expression classifier achieved an accuracy of 70% compared to 85% using MRI. Bootstrapping validation produced expression and MRI classifiers with mean accuracies of 76% and 82%, respectively, demonstrating better concordance between these two classifiers than achieved in a single validation population. We conclude there is potential for blood expression to be a marker for AD. The classifier also predicts a large number of people with MCI, who are likely to develop AD, are more AD-like than normal with 76% of subjects classified as AD rather than control. Many of these people do not have overt brain atrophy, which is known to emerge around the time of AD diagnosis, suggesting the expression classifier may detect AD earlier in the prodromal phase. However, we accept these results could also represent a marker of diseases sharing common etiology.
authors.affiliation: King's College London, Institute of Psychiatry, King's Health Partners Centre for Neurodegeneration Research, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Lunnon
authors.forename: Martina
authors.initials: M
authors.lastname: Sattlecker
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Furney
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Lupton
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.forename: Caroline
authors.initials: C
authors.lastname: Johnston
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Daniel
authors.initials: D
authors.lastname: Geschwind
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.forename: Angela
authors.initials: A
authors.lastname: Hodges
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism*; D003072:Cognition Disorders / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins