Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

Paolo Reho; Sara Saez-Atienzar; Paola Ruffo; Sultana Solaiman; Zalak Shah; Ruth Chia; Karri Kaivola; Bryan J. Traynor; Bension S. Tilley; Steve M. Gentleman; Angela K. Hodges; Dag Aarsland; Edwin S. Monuki; Kathy L. Newell; Randy Woltjer; Marilyn S. Albert; Ted M. Dawson; Liana S. Rosenthal; Juan C. Troncoso; Olga Pletnikova; Geidy E. Serrano; Thomas G. Beach; Hariharan P. Easwaran; Sonja W. Scholz

doi:10.1038/s42003-023-05725-x

Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

Paolo Reho, Sara Saez-Atienzar, Paola Ruffo, Sultana Solaiman, Zalak Shah, Ruth Chia, Karri Kaivola, Bryan J. Traynor, Bension S. Tilley, Steve M. Gentleman, Angela K. Hodges, Dag Aarsland, Edwin S. Monuki, Kathy L. Newell, Randy Woltjer, Marilyn S. Albert, Ted M. Dawson, Liana S. Rosenthal, Juan C. Troncoso, Olga PletnikovaGeidy E. Serrano, Thomas G. Beach, Hariharan P. Easwaran, Sonja W. Scholz

Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.

Original language	English (US)
Article number	35
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-05725-x
State	Published - Dec 2024

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Reho, P., Saez-Atienzar, S., Ruffo, P., Solaiman, S., Shah, Z., Chia, R., Kaivola, K., Traynor, B. J., Tilley, B. S., Gentleman, S. M., Hodges, A. K., Aarsland, D., Monuki, E. S., Newell, K. L., Woltjer, R., Albert, M. S., Dawson, T. M., Rosenthal, L. S., Troncoso, J. C., ... Scholz, S. W. (2024). Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies. Communications Biology, 7(1), Article 35. https://doi.org/10.1038/s42003-023-05725-x

Reho, P, Saez-Atienzar, S, Ruffo, P, Solaiman, S, Shah, Z, Chia, R, Kaivola, K, Traynor, BJ, Tilley, BS, Gentleman, SM, Hodges, AK, Aarsland, D, Monuki, ES, Newell, KL, Woltjer, R, Albert, MS, Dawson, TM, Rosenthal, LS, Troncoso, JC, Pletnikova, O, Serrano, GE, Beach, TG, Easwaran, HP & Scholz, SW 2024, 'Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies', Communications Biology, vol. 7, no. 1, 35. https://doi.org/10.1038/s42003-023-05725-x

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title = "Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies",

abstract = "Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.",

author = "Paolo Reho and Sara Saez-Atienzar and Paola Ruffo and Sultana Solaiman and Zalak Shah and Ruth Chia and Karri Kaivola and Traynor, {Bryan J.} and Tilley, {Bension S.} and Gentleman, {Steve M.} and Hodges, {Angela K.} and Dag Aarsland and Monuki, {Edwin S.} and Newell, {Kathy L.} and Randy Woltjer and Albert, {Marilyn S.} and Dawson, {Ted M.} and Rosenthal, {Liana S.} and Troncoso, {Juan C.} and Olga Pletnikova and Serrano, {Geidy E.} and Beach, {Thomas G.} and Easwaran, {Hariharan P.} and Scholz, {Sonja W.}",

note = "Publisher Copyright: {\textcopyright} 2024, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2024",

month = dec,

doi = "10.1038/s42003-023-05725-x",

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T1 - Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

AU - Reho, Paolo

AU - Saez-Atienzar, Sara

AU - Ruffo, Paola

AU - Solaiman, Sultana

AU - Shah, Zalak

AU - Chia, Ruth

AU - Kaivola, Karri

AU - Traynor, Bryan J.

AU - Tilley, Bension S.

AU - Gentleman, Steve M.

AU - Hodges, Angela K.

AU - Aarsland, Dag

AU - Monuki, Edwin S.

AU - Newell, Kathy L.

AU - Woltjer, Randy

AU - Albert, Marilyn S.

AU - Dawson, Ted M.

AU - Rosenthal, Liana S.

AU - Troncoso, Juan C.

AU - Pletnikova, Olga

AU - Serrano, Geidy E.

AU - Beach, Thomas G.

AU - Easwaran, Hariharan P.

AU - Scholz, Sonja W.

PY - 2024/12

Y1 - 2024/12

N2 - Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.

AB - Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.

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Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

Abstract

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