Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer's disease

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• 作者：Kuang-Den Chen^a ; Po-Tsung Chang^b ; Yueh-Hsin Ping^c ; Hsin-Chen Lee^c ; Chin-Wei Yeh^a ; Pei-Ning Wang^d ; ^e ; ^{pnwang@vghtpe.gov.tw"" rel=""nofollow}
• 关键词：Gene expression profile ; ABCB1 ; Peripheral blood leukocytes ; Microarray ; Alzheimer's disease ; Mild cognitive impairment
• 刊名：Neurobiology of Disease
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：43
• 期：3
• 页码：698-705
• 全文大小：339 K

文摘

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&#xa0;<&#xa0;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&#xa0;=&#xa0;0.3858, p&#xa0;=&#xa0;0.0011). With a limited number of study population, our study may provide a novel direction for evaluating diagnostic biomarkers in monitoring AD progression.