Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23042217
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.
DATE PUBLISHED
2013
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/10/09 06:00
pubmed 2012/10/09 06:00
medline 2013/06/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lunnon K Lunnon Katie K King's College London, Institute of Psychiatry, King's Health Partners Centre for Neurodegeneration Research, London, UK.
Sattlecker M Sattlecker Martina M
Furney SJ Furney Simon J SJ
Coppola G Coppola Giovanni G
Simmons A Simmons Andrew A
Proitsi P Proitsi Petroula P
Lupton MK Lupton Michelle K MK
Lourdusamy A Lourdusamy Anbarasu A
Johnston C Johnston Caroline C
Soininen H Soininen Hilkka H
KÅ‚oszewska I KÅ‚oszewska Iwona I
Mecocci P Mecocci Patrizia P
Tsolaki M Tsolaki Magda M
Vellas B Vellas Bruno B
Geschwind D Geschwind Daniel D
Lovestone S Lovestone Simon S
Dobson R Dobson Richard R
Hodges A Hodges Angela A
dNeuroMed Consortium
INVESTIGATORS
JOURNAL
VOLUME: 33
ISSUE: 3
TITLE: Journal of Alzheimer's disease : JAD
ISOABBREVIATION: J. Alzheimers Dis.
YEAR: 2013
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1875-8908
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Alzheimers Dis
COUNTRY: Netherlands
ISSNLINKING: 1387-2877
NLMUNIQUEID: 9814863
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
1RC1AG035610 NIA NIH HHS United States
G0801464 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Alzheimer Disease genetics
Apolipoproteins E genetics
Blood Proteins metabolism
Cognition Disorders blood
Female blood
Gene Expression Profiling blood
Humans blood
Magnetic Resonance Imaging blood
Male blood
Middle Aged blood
Oligonucleotide Array Sequence Analysis blood
Predictive Value of Tests blood
Psychiatric Status Rating Scales blood
Retrospective Studies blood
Sensitivity and Specificity blood
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Apolipoproteins E
0 Blood Proteins
OTHER ID's