title: Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer's disease.
abstract: Increasing evidence has shown that the immunological reaction of leukocytes plays a crucial role in the development of neurodegenerative disorders. We conducted transcriptome analysis of leukocytes from patients of mild cognitive impairment (MCI), Alzheimer's disease (AD), as well as normal controls (NC) by oligonucleotide microarray. The differentially expressed genes of interest were selected by pathway-based functional enrichment and were then validated in 60 subjects (17 NC, 20 MCI and 23 AD) by quantitative PCR (QRT-PCR). Thirty-four differentially expressed genes between NC and AD were enriched in ATP-binding cassette (ABC) transporters, ascorbate and aldarate metabolism, Gly/Ser/Thr metabolism, transforming growth factor-β signaling, and extracellular matrix (ECM)-receptor interaction pathways (Welch t-test; p < 0.05). Comparison of NC, MCI and AD transcriptomes identified 8 genes significantly associated with purine metabolism and the ABC transporters. Furthermore, 13 out of 18 genes selected from the above lists were successfully validated by QRT-PCR (Mann-Whitney U-test), and only ABCB1 gene exhibited significantly positive correlation with MMSE scores among NC, MCI, and AD subjects (r = 0.3858, p = 0.0011). With a limited number of study population, our study may provide a novel direction for evaluating diagnostic biomarkers in monitoring AD progression.
authors.affiliation: Center for Translational Research in Biomedical Sciences, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.forename: Po-Tsung
authors.initials: PT
authors.lastname: Chang
authors.forename: Yueh-Hsin
authors.initials: YH
authors.lastname: Ping
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Yeh
authors.forename: Pei-Ning
authors.initials: PN
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics*; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000592:standards*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods / Q000592:standards*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000592:standards; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005819:Genetic Markers