Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain

Aliza P. Wingo; Wen Fan; Duc M. Duong; Ekaterina S. Gerasimov; Eric B. Dammer; Yue Liu; Nadia V. Harerimana; Bartholomew White; Madhav Thambisetty; Juan C. Troncoso; Namhee Kim; Julie A. Schneider; Ihab M. Hajjar; James J. Lah; David A. Bennett; Nicholas T. Seyfried; Allan I. Levey; Thomas S. Wingo

doi:10.1038/s41593-020-0635-5

Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain

Aliza P. Wingo, Wen Fan, Duc M. Duong, Ekaterina S. Gerasimov, Eric B. Dammer, Yue Liu, Nadia V. Harerimana, Bartholomew White, Madhav Thambisetty, Juan C. Troncoso, Namhee Kim, Julie A. Schneider, Ihab M. Hajjar, James J. Lah, David A. Bennett, Nicholas T. Seyfried, Allan I. Levey, Thomas S. Wingo

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

71 Scopus citations

Abstract

Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and between RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer’s disease, suggesting shared mechanisms.

Original language	English (US)
Pages (from-to)	696-700
Number of pages	5
Journal	Nature neuroscience
Volume	23
Issue number	6
DOIs	https://doi.org/10.1038/s41593-020-0635-5
State	Published - Jun 1 2020
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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Wingo, A. P., Fan, W., Duong, D. M., Gerasimov, E. S., Dammer, E. B., Liu, Y., Harerimana, N. V., White, B., Thambisetty, M., Troncoso, J. C., Kim, N., Schneider, J. A., Hajjar, I. M., Lah, J. J., Bennett, D. A., Seyfried, N. T., Levey, A. I., & Wingo, T. S. (2020). Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain. Nature neuroscience, 23(6), 696-700. https://doi.org/10.1038/s41593-020-0635-5

Wingo, AP, Fan, W, Duong, DM, Gerasimov, ES, Dammer, EB, Liu, Y, Harerimana, NV, White, B, Thambisetty, M, Troncoso, JC, Kim, N, Schneider, JA, Hajjar, IM, Lah, JJ, Bennett, DA, Seyfried, NT, Levey, AI & Wingo, TS 2020, 'Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain', Nature neuroscience, vol. 23, no. 6, pp. 696-700. https://doi.org/10.1038/s41593-020-0635-5

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abstract = "Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and between RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer{\textquoteright}s disease, suggesting shared mechanisms.",

author = "Wingo, {Aliza P.} and Wen Fan and Duong, {Duc M.} and Gerasimov, {Ekaterina S.} and Dammer, {Eric B.} and Yue Liu and Harerimana, {Nadia V.} and Bartholomew White and Madhav Thambisetty and Troncoso, {Juan C.} and Namhee Kim and Schneider, {Julie A.} and Hajjar, {Ihab M.} and Lah, {James J.} and Bennett, {David A.} and Seyfried, {Nicholas T.} and Levey, {Allan I.} and Wingo, {Thomas S.}",

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AU - Duong, Duc M.

AU - Gerasimov, Ekaterina S.

AU - Dammer, Eric B.

AU - Liu, Yue

AU - Harerimana, Nadia V.

AU - White, Bartholomew

AU - Thambisetty, Madhav

AU - Troncoso, Juan C.

AU - Kim, Namhee

AU - Schneider, Julie A.

AU - Hajjar, Ihab M.

AU - Lah, James J.

AU - Bennett, David A.

AU - Seyfried, Nicholas T.

AU - Levey, Allan I.

AU - Wingo, Thomas S.

PY - 2020/6/1

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AB - Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and between RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer’s disease, suggesting shared mechanisms.

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Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain

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