Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes

Jeroen G J van Rooij; Lieke H H Meeter; Shami Melhem; Diana A T Nijholt; Tsz Hang Wong; Annemieke Rozemuller; Andre G Uitterlinden; Joyce G van Meurs; John C van Swieten

doi:10.1016/j.neurobiolaging.2018.10.023

Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes

Jeroen G J van Rooij, Lieke H H Meeter, Shami Melhem, Diana A T Nijholt, Tsz Hang Wong, , Annemieke Rozemuller, Andre G Uitterlinden, Joyce G van Meurs, John C van Swieten

Netherlands Institute for Neuroscience (NIN)

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Abstract

Knowledge about the molecular mechanisms driving Alzheimer's disease (AD) is still limited. To learn more about AD biology, we performed whole transcriptome sequencing on the hippocampus of 20 AD cases and 10 age- and sex-matched cognitively healthy controls. We observed 2716 differentially expressed genes, of which 48% replicated in a second data set of 84 AD cases and 33 controls. We used an integrative network-based approach for combining transcriptomic and protein-protein interaction data to find differentially expressed gene modules that may reflect key processes in AD biology. A total of 735 differentially expressed genes were clustered into 33 modules, of which 82% replicated in a second data set, highlighting the robustness of this approach. These 27 modules were enriched for signal transduction, transport, response to stimulus, and several organic and cellular metabolic pathways. Ten modules interacted with previously described AD genes. Our study indicates that analyzing RNA-expression data based on annotated gene modules is more robust than on individual genes. We provide a comprehensive overview of the biological processes involved in AD, and the detected differentially expressed gene modules may provide a molecular basis for future research into mechanisms underlying AD.

Original language	English
Pages (from-to)	225-233
Number of pages	9
Journal	Neurobiology of Aging
Volume	74
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.10.023
Publication status	Published - 2019

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VanRooij2019NeuroBiolAgingFinal published version, 1.51 MBLicence: CC BY-NC-ND

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van Rooij, J. G. J., Meeter, L. H. H., Melhem, S., Nijholt, D. A. T., Wong, T. H., Rozemuller, A., Uitterlinden, A. G., & van Meurs, J. G., & van Swieten, J. C. (2019). Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes. Neurobiology of Aging, 74, 225-233. https://doi.org/10.1016/j.neurobiolaging.2018.10.023

van Rooij, Jeroen G J ; Meeter, Lieke H H ; Melhem, Shami ; Nijholt, Diana A T ; Wong, Tsz Hang ; Rozemuller, Annemieke ; Uitterlinden, Andre G ; van Meurs, Joyce G ; van Swieten, John C. / Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes. In: Neurobiology of Aging. 2019 ; Vol. 74. pp. 225-233.

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title = "Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes",

abstract = "Knowledge about the molecular mechanisms driving Alzheimer's disease (AD) is still limited. To learn more about AD biology, we performed whole transcriptome sequencing on the hippocampus of 20 AD cases and 10 age- and sex-matched cognitively healthy controls. We observed 2716 differentially expressed genes, of which 48% replicated in a second data set of 84 AD cases and 33 controls. We used an integrative network-based approach for combining transcriptomic and protein-protein interaction data to find differentially expressed gene modules that may reflect key processes in AD biology. A total of 735 differentially expressed genes were clustered into 33 modules, of which 82% replicated in a second data set, highlighting the robustness of this approach. These 27 modules were enriched for signal transduction, transport, response to stimulus, and several organic and cellular metabolic pathways. Ten modules interacted with previously described AD genes. Our study indicates that analyzing RNA-expression data based on annotated gene modules is more robust than on individual genes. We provide a comprehensive overview of the biological processes involved in AD, and the detected differentially expressed gene modules may provide a molecular basis for future research into mechanisms underlying AD.",

author = "{van Rooij}, {Jeroen G J} and Meeter, {Lieke H H} and Shami Melhem and Nijholt, {Diana A T} and Wong, {Tsz Hang} and I. Huitinga and Annemieke Rozemuller and Uitterlinden, {Andre G} and {van Meurs}, {Joyce G} and {van Swieten}, {John C}",

year = "2019",

doi = "10.1016/j.neurobiolaging.2018.10.023",

language = "English",

volume = "74",

pages = "225--233",

journal = "Neurobiology of Aging",

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van Rooij, JGJ, Meeter, LHH, Melhem, S, Nijholt, DAT, Wong, TH, Rozemuller, A, Uitterlinden, AG & van Meurs, JG & van Swieten, JC 2019, 'Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes', Neurobiology of Aging, vol. 74, pp. 225-233. https://doi.org/10.1016/j.neurobiolaging.2018.10.023

Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes. / van Rooij, Jeroen G J; Meeter, Lieke H H; Melhem, Shami; Nijholt, Diana A T; Wong, Tsz Hang; Rozemuller, Annemieke; Uitterlinden, Andre G; van Meurs, Joyce G; van Swieten, John C.

In: Neurobiology of Aging, Vol. 74, 2019, p. 225-233.

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

TY - JOUR

T1 - Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes

AU - van Rooij, Jeroen G J

AU - Meeter, Lieke H H

AU - Melhem, Shami

AU - Nijholt, Diana A T

AU - Wong, Tsz Hang

AU - Huitinga, I.

AU - Rozemuller, Annemieke

AU - Uitterlinden, Andre G

AU - van Meurs, Joyce G

AU - van Swieten, John C

PY - 2019

Y1 - 2019

N2 - Knowledge about the molecular mechanisms driving Alzheimer's disease (AD) is still limited. To learn more about AD biology, we performed whole transcriptome sequencing on the hippocampus of 20 AD cases and 10 age- and sex-matched cognitively healthy controls. We observed 2716 differentially expressed genes, of which 48% replicated in a second data set of 84 AD cases and 33 controls. We used an integrative network-based approach for combining transcriptomic and protein-protein interaction data to find differentially expressed gene modules that may reflect key processes in AD biology. A total of 735 differentially expressed genes were clustered into 33 modules, of which 82% replicated in a second data set, highlighting the robustness of this approach. These 27 modules were enriched for signal transduction, transport, response to stimulus, and several organic and cellular metabolic pathways. Ten modules interacted with previously described AD genes. Our study indicates that analyzing RNA-expression data based on annotated gene modules is more robust than on individual genes. We provide a comprehensive overview of the biological processes involved in AD, and the detected differentially expressed gene modules may provide a molecular basis for future research into mechanisms underlying AD.

AB - Knowledge about the molecular mechanisms driving Alzheimer's disease (AD) is still limited. To learn more about AD biology, we performed whole transcriptome sequencing on the hippocampus of 20 AD cases and 10 age- and sex-matched cognitively healthy controls. We observed 2716 differentially expressed genes, of which 48% replicated in a second data set of 84 AD cases and 33 controls. We used an integrative network-based approach for combining transcriptomic and protein-protein interaction data to find differentially expressed gene modules that may reflect key processes in AD biology. A total of 735 differentially expressed genes were clustered into 33 modules, of which 82% replicated in a second data set, highlighting the robustness of this approach. These 27 modules were enriched for signal transduction, transport, response to stimulus, and several organic and cellular metabolic pathways. Ten modules interacted with previously described AD genes. Our study indicates that analyzing RNA-expression data based on annotated gene modules is more robust than on individual genes. We provide a comprehensive overview of the biological processes involved in AD, and the detected differentially expressed gene modules may provide a molecular basis for future research into mechanisms underlying AD.

U2 - 10.1016/j.neurobiolaging.2018.10.023

DO - 10.1016/j.neurobiolaging.2018.10.023

M3 - Article

C2 - 30497016

VL - 74

SP - 225

EP - 233

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -

Hippocampal transcriptome profiling combined with protein-protein interaction analysis elucidates Alzheimer's disease pathways and genes

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