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

• Published in: Neurobiology of disease Vol. 43; no. 3; pp. 698 - 705
• Main Authors: Chen, Kuang-Den, Chang, Po-Tsung, Ping, Yueh-Hsin, Lee, Hsin-Chen, Yeh, Chin-Wei, Wang, Pei-Ning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2011; Elsevier
• Subjects: ABCB1; Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Female; Gene expression profile; Gene Expression Profiling - methods; Gene Expression Profiling - standards; Genetic Markers - genetics; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Testing - methods; Genetic Testing - standards; Humans; Leukocytes - physiology; Male; Microarray; Mild cognitive impairment; Neurology; Oligonucleotide Array Sequence Analysis - methods; Oligonucleotide Array Sequence Analysis - standards; Peripheral blood leukocytes; Predictive Value of Tests; Reproducibility of Results; Risk Factors; ABCB1; Peripheral blood leukocytes; Microarray; Mild cognitive impairment; Alzheimer's disease; Gene expression profile
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2011.05.023

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. ► Relatively high success rate (72%) in validation by using pathway-based gene selection. ► Strong association of the ABC transporter category with MCI and AD was observed. ► The expression levels of ABCB1 were positively associated with the MMSE scores of study population. ► Our approach serves as a new way to examine molecular abnormalities in leukocytes.