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. 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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 ADpatients 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 ADpatients 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 ADpatients: 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. 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Authors: Bartholomew J Naughton; F Jason Duncan; Darren A Murrey; Aaron S Meadows; David E Newsom; Nicoleta Stoicea; Peter White; Douglas W Scharre; Douglas M Mccarty; Haiyan Fu Journal: J Alzheimers Dis Date: 2015 Impact factor: 4.472
Authors: Madhav Thambisetty; Romina Tripaldi; Joanna Riddoch-Contreras; Abdul Hye; Yang An; James Campbell; Jitka Sojkova; Anna Kinsey; Steven Lynham; Yun Zhou; Luigi Ferrucci; Dean F Wong; Simon Lovestone; Susan M Resnick Journal: J Alzheimers Dis Date: 2010 Impact factor: 4.472