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Toward an Alzheimer's disease diagnosis via high‐resolution blood gene expression
Author(s) -
Fehlbaum-Beurdeley Pascale,
Jarrige-Le Prado Anne Charlotte,
Pallares Diego,
Carrière Jennifer,
Guihal Caroline,
Soucaille Cyril,
Rouet Fabien,
Drouin Dominique,
Sol Olivier,
Jordan Heather,
Wu Darong,
Lei Ling,
Einstein Richard,
Schweighoffer Fabien,
Bracco Laurent
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.07.001
Subject(s) - transcriptome , disease , biology , dementia , gene , gene expression profiling , inflammation , gene expression , alzheimer's disease , bioinformatics , computational biology , immunology , medicine , genetics
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‐β) 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.