Toward an Alzheimer's disease diagnosis via high-resolution blood gene expression.
BACKGROUND
There is a significant need for reliable molecular biomarkers to aid in Alzheimer's disease (AD) clinical diagnosis.


METHODS
We performed a genome-wide investigation of the human transcriptome, taking into account the discriminatory power of splice variations from the blood of 80 AD patients and 70 nondemented control (NDC) individuals.


RESULTS
We characterized a blood RNA signature composed of 170 oligonucleotide probe sets associated with 133 genes that can correctly distinguish AD patients from NDC with a sensitivity of 100% and specificity of 96%. Functionally, this signature highlights genes involved in pathways that were associated with macrophages and lymphocytes within AD patients: Transforming growth factor (TGF-beta) signaling, oxidative stress, innate immunity and inflammation, cholesterol homeostasis, and lipid-raft perturbation, whereas other genes may also provide new insights in the biology of AD.


CONCLUSIONS
This study provides proof-of-concept that whole-blood profiling can generate an AD-associated classification signature via the specific relative expression of biologically relevant RNAs. Such a signature will need to be validated with extended patient cohorts, and evaluated to learn whether it can differentiate AD from others types of dementia.
Fehlbaum-Beurdeley
Pascale
P
ExonHit Therapeutics, Paris, France. pascale.beurdeley@exonhit.com
Jarrige-Le Prado
Anne Charlotte
AC
Pallares
Diego
D
Carrière
Jennifer
J
Guihal
Caroline
C
Soucaille
Cyril
C
Rouet
Fabien
F
Drouin
Dominique
D
Sol
Olivier
O
Jordan
Heather
H
Wu
Darong
D
Lei
Ling
L
Einstein
Richard
R
Schweighoffer
Fabien
F
Bracco
Laurent
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D008609:Mental Status Schedule; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000097:blood*
D002800:Cholinesterase Inhibitors; D016212:Transforming Growth Factor beta