Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis

Jean Pierre Roussarie; Vicky Yao; Patricia Rodriguez-Rodriguez; Rose Oughtred; Jennifer Rust; Zakary Plautz; Shirin Kasturia; Christian Albornoz; Wei Wang; Eric F. Schmidt; Ruth Dannenfelser; Alicja Tadych; Lars Brichta; Alona Barnea-Cramer; Nathaniel Heintz; Patrick R. Hof; Myriam Heiman; Kara Dolinski; Marc Flajolet; Olga G. Troyanskaya; Paul Greengard

doi:10.1016/j.neuron.2020.06.010

Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis

Jean Pierre Roussarie, Vicky Yao, Patricia Rodriguez-Rodriguez, Rose Oughtred, Jennifer Rust, Zakary Plautz, Shirin Kasturia, Christian Albornoz, Wei Wang, Eric F. Schmidt, Ruth Dannenfelser, Alicja Tadych, Lars Brichta, Alona Barnea-Cramer, Nathaniel Heintz, Patrick R. Hof, Myriam Heiman, Kara Dolinski, Marc Flajolet, Olga G. TroyanskayaPaul Greengard

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

61 Scopus citations

Abstract

Neurons display different levels of vulnerability to Alzheimer's pathology. Roussarie et al. experimentally profile and computationally model several relevant neuron types. Using a mouse-human framework, they identify genes linking Aß, aging, and tau in vulnerable neurons. Finally, they show experimentally that PTB, a regulator of tau splicing, contributes to vulnerability.

Original language	English (US)
Pages (from-to)	821-835.e12
Journal	Neuron
Volume	107
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2020.06.010
State	Published - Sep 9 2020

All Science Journal Classification (ASJC) codes

Neuroscience(all)

Keywords

Alzheimer's disease
PTBP1
bacTRAP
machine learning
network
selective neuronal vulnerability

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10.1016/j.neuron.2020.06.010

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Roussarie, J. P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., Kasturia, S., Albornoz, C., Wang, W., Schmidt, E. F., Dannenfelser, R., Tadych, A., Brichta, L., Barnea-Cramer, A., Heintz, N., Hof, P. R., Heiman, M., Dolinski, K., Flajolet, M., ... Greengard, P. (2020). Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis. Neuron, 107(5), 821-835.e12. https://doi.org/10.1016/j.neuron.2020.06.010

@article{f6cbad867d0145b2949050f7add7fba4,

title = "Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis",

abstract = "Neurons display different levels of vulnerability to Alzheimer's pathology. Roussarie et al. experimentally profile and computationally model several relevant neuron types. Using a mouse-human framework, they identify genes linking A{\ss}, aging, and tau in vulnerable neurons. Finally, they show experimentally that PTB, a regulator of tau splicing, contributes to vulnerability.",

keywords = "Alzheimer's disease, PTBP1, bacTRAP, machine learning, network, selective neuronal vulnerability",

author = "Roussarie, {Jean Pierre} and Vicky Yao and Patricia Rodriguez-Rodriguez and Rose Oughtred and Jennifer Rust and Zakary Plautz and Shirin Kasturia and Christian Albornoz and Wei Wang and Schmidt, {Eric F.} and Ruth Dannenfelser and Alicja Tadych and Lars Brichta and Alona Barnea-Cramer and Nathaniel Heintz and Hof, {Patrick R.} and Myriam Heiman and Kara Dolinski and Marc Flajolet and Troyanskaya, {Olga G.} and Paul Greengard",

note = "Funding Information: We thank A. Milosevic, R. Chottekalapanda, H. Rebholz, M. Riessland, B. Kolisnyk, R. Sealfon, C. Theesfeld, and R. Zhang for critical reading of the manuscript; E. Griggs for assistance with graphic design; R. Norinsky and Rockefeller University (RU) Transgenic Services for all pronuclear injections; C. Zhao and the RU Genomics Resource Center for all sequencing; and the RU Bioimaging Resource Center. J.-P.R. M.F. and P.G. were supported by the Fisher Center for Alzheimer's Disease Research. V.Y. was supported in part by NIH grant T32 HG003284. O.G.T. is a senior fellow of the Genetic Networks Program of the Canadian Institute for Advanced Research (CIFAR). P.R.-R. was supported in part by the European Union Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 799638. This study was supported by the JPB Foundation and Cure Alzheimer's Fund (to P.G. and M.H.), United States Army Medical Research and Material Command (USAMRMC) award W81XWH-14-1-0046 (to J.-P.R.), the National Institute on Aging of the NIH (awards RF1AG047779 to P.G. and J.-P.R.; RF1AG054564 to P.G. J.-P.R. and A.B.-C.; and P50 AG005138 to P.R.H.), NIH R01 GM071966 (to O.G.T.), the Office of Research Infrastructure Programs of the NIH (award R01OD010929 to K.D.), the National Institute of Neurological Disorders and Stroke of the NIH (award R01NS091722 to E.F.S.), and the Howard Hughes Medical Institute (to N.H.). The results published here are in part based on data obtained from Agora, a platform initially developed by the NIA-funded AMP-AD Consortium. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the sponsors. J.-P.R. V.Y. O.G.T. and P.G. conceived and designed the research with input from M.H. and P.R.H. J.-P.R. generated mice with help from E.F.S. N.H. and L.B. J.-P.R. S.K. and C.A. performed bacTRAP experiments. P.R.-R. and Z.P. performed stereotaxic injections. V.Y. and O.G.T. conceived the computational analyses. V.Y. performed all bacTRAP data analyses, generated and analyzed functional networks, reprioritized genes, and re-analyzed publicly available datasets. W.W. performed some additional RNA-seq experiments. V.Y. and J.-P.R. analyzed results from the computational analyses. M.F. R.O. J.R. and K.D. curated amyloid and NFT lists. V.Y. R.D. and A.T. made the data available at http://alz.princeton.edu. J.-P.R. V.Y. O.G.T. and P.G. wrote the manuscript with input from M.F. P.R.H. P.R.-R. and A.B.-C. The authors declare no competing interests. Funding Information: We thank A. Milosevic, R. Chottekalapanda, H. Rebholz, M. Riessland, B. Kolisnyk, R. Sealfon, C. Theesfeld, and R. Zhang for critical reading of the manuscript; E. Griggs for assistance with graphic design; R. Norinsky and Rockefeller University (RU) Transgenic Services for all pronuclear injections; C. Zhao and the RU Genomics Resource Center for all sequencing; and the RU Bioimaging Resource Center. J.-P.R., M.F., and P.G. were supported by the Fisher Center for Alzheimer{\textquoteright}s Disease Research . V.Y. was supported in part by NIH grant T32 HG003284 . O.G.T. is a senior fellow of the Genetic Networks Program of the Canadian Institute for Advanced Research (CIFAR). P.R.-R. was supported in part by the European Union Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 799638 . This study was supported by the JPB Foundation and Cure Alzheimer's Fund (to P.G. and M.H.), United States Army Medical Research and Material Command (USAMRMC) award W81XWH-14-1-0046 (to J.-P.R.), the National Institute on Aging of the NIH (awards RF1AG047779 to P.G. and J.-P.R.; RF1AG054564 to P.G., J.-P.R., and A.B.-C.; and P50 AG005138 to P.R.H.), NIH R01 GM071966 (to O.G.T.), the Office of Research Infrastructure Programs of the NIH (award R01OD010929 to K.D.), the National Institute of Neurological Disorders and Stroke of the NIH (award R01NS091722 to E.F.S.), and the Howard Hughes Medical Institute (to N.H.). The results published here are in part based on data obtained from Agora, a platform initially developed by the NIA-funded AMP-AD Consortium. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the sponsors. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = sep,

day = "9",

doi = "10.1016/j.neuron.2020.06.010",

language = "English (US)",

volume = "107",

pages = "821--835.e12",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "5",

}

Roussarie, JP, Yao, V, Rodriguez-Rodriguez, P, Oughtred, R, Rust, J, Plautz, Z, Kasturia, S, Albornoz, C, Wang, W, Schmidt, EF, Dannenfelser, R, Tadych, A, Brichta, L, Barnea-Cramer, A, Heintz, N, Hof, PR, Heiman, M, Dolinski, K, Flajolet, M, Troyanskaya, OG & Greengard, P 2020, 'Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis', Neuron, vol. 107, no. 5, pp. 821-835.e12. https://doi.org/10.1016/j.neuron.2020.06.010

TY - JOUR

T1 - Selective Neuronal Vulnerability in Alzheimer's Disease

T2 - A Network-Based Analysis

AU - Roussarie, Jean Pierre

AU - Yao, Vicky

AU - Rodriguez-Rodriguez, Patricia

AU - Oughtred, Rose

AU - Rust, Jennifer

AU - Plautz, Zakary

AU - Kasturia, Shirin

AU - Albornoz, Christian

AU - Wang, Wei

AU - Schmidt, Eric F.

AU - Dannenfelser, Ruth

AU - Tadych, Alicja

AU - Brichta, Lars

AU - Barnea-Cramer, Alona

AU - Heintz, Nathaniel

AU - Hof, Patrick R.

AU - Heiman, Myriam

AU - Dolinski, Kara

AU - Flajolet, Marc

AU - Troyanskaya, Olga G.

AU - Greengard, Paul

N1 - Funding Information: We thank A. Milosevic, R. Chottekalapanda, H. Rebholz, M. Riessland, B. Kolisnyk, R. Sealfon, C. Theesfeld, and R. Zhang for critical reading of the manuscript; E. Griggs for assistance with graphic design; R. Norinsky and Rockefeller University (RU) Transgenic Services for all pronuclear injections; C. Zhao and the RU Genomics Resource Center for all sequencing; and the RU Bioimaging Resource Center. J.-P.R. M.F. and P.G. were supported by the Fisher Center for Alzheimer's Disease Research. V.Y. was supported in part by NIH grant T32 HG003284. O.G.T. is a senior fellow of the Genetic Networks Program of the Canadian Institute for Advanced Research (CIFAR). P.R.-R. was supported in part by the European Union Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 799638. This study was supported by the JPB Foundation and Cure Alzheimer's Fund (to P.G. and M.H.), United States Army Medical Research and Material Command (USAMRMC) award W81XWH-14-1-0046 (to J.-P.R.), the National Institute on Aging of the NIH (awards RF1AG047779 to P.G. and J.-P.R.; RF1AG054564 to P.G. J.-P.R. and A.B.-C.; and P50 AG005138 to P.R.H.), NIH R01 GM071966 (to O.G.T.), the Office of Research Infrastructure Programs of the NIH (award R01OD010929 to K.D.), the National Institute of Neurological Disorders and Stroke of the NIH (award R01NS091722 to E.F.S.), and the Howard Hughes Medical Institute (to N.H.). The results published here are in part based on data obtained from Agora, a platform initially developed by the NIA-funded AMP-AD Consortium. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the sponsors. J.-P.R. V.Y. O.G.T. and P.G. conceived and designed the research with input from M.H. and P.R.H. J.-P.R. generated mice with help from E.F.S. N.H. and L.B. J.-P.R. S.K. and C.A. performed bacTRAP experiments. P.R.-R. and Z.P. performed stereotaxic injections. V.Y. and O.G.T. conceived the computational analyses. V.Y. performed all bacTRAP data analyses, generated and analyzed functional networks, reprioritized genes, and re-analyzed publicly available datasets. W.W. performed some additional RNA-seq experiments. V.Y. and J.-P.R. analyzed results from the computational analyses. M.F. R.O. J.R. and K.D. curated amyloid and NFT lists. V.Y. R.D. and A.T. made the data available at http://alz.princeton.edu. J.-P.R. V.Y. O.G.T. and P.G. wrote the manuscript with input from M.F. P.R.H. P.R.-R. and A.B.-C. The authors declare no competing interests. Funding Information: We thank A. Milosevic, R. Chottekalapanda, H. Rebholz, M. Riessland, B. Kolisnyk, R. Sealfon, C. Theesfeld, and R. Zhang for critical reading of the manuscript; E. Griggs for assistance with graphic design; R. Norinsky and Rockefeller University (RU) Transgenic Services for all pronuclear injections; C. Zhao and the RU Genomics Resource Center for all sequencing; and the RU Bioimaging Resource Center. J.-P.R., M.F., and P.G. were supported by the Fisher Center for Alzheimer’s Disease Research . V.Y. was supported in part by NIH grant T32 HG003284 . O.G.T. is a senior fellow of the Genetic Networks Program of the Canadian Institute for Advanced Research (CIFAR). P.R.-R. was supported in part by the European Union Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie grant agreement 799638 . This study was supported by the JPB Foundation and Cure Alzheimer's Fund (to P.G. and M.H.), United States Army Medical Research and Material Command (USAMRMC) award W81XWH-14-1-0046 (to J.-P.R.), the National Institute on Aging of the NIH (awards RF1AG047779 to P.G. and J.-P.R.; RF1AG054564 to P.G., J.-P.R., and A.B.-C.; and P50 AG005138 to P.R.H.), NIH R01 GM071966 (to O.G.T.), the Office of Research Infrastructure Programs of the NIH (award R01OD010929 to K.D.), the National Institute of Neurological Disorders and Stroke of the NIH (award R01NS091722 to E.F.S.), and the Howard Hughes Medical Institute (to N.H.). The results published here are in part based on data obtained from Agora, a platform initially developed by the NIA-funded AMP-AD Consortium. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the sponsors. Publisher Copyright: © 2020 The Authors

PY - 2020/9/9

Y1 - 2020/9/9

N2 - Neurons display different levels of vulnerability to Alzheimer's pathology. Roussarie et al. experimentally profile and computationally model several relevant neuron types. Using a mouse-human framework, they identify genes linking Aß, aging, and tau in vulnerable neurons. Finally, they show experimentally that PTB, a regulator of tau splicing, contributes to vulnerability.

AB - Neurons display different levels of vulnerability to Alzheimer's pathology. Roussarie et al. experimentally profile and computationally model several relevant neuron types. Using a mouse-human framework, they identify genes linking Aß, aging, and tau in vulnerable neurons. Finally, they show experimentally that PTB, a regulator of tau splicing, contributes to vulnerability.

KW - Alzheimer's disease

KW - PTBP1

KW - bacTRAP

KW - machine learning

KW - network

KW - selective neuronal vulnerability

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M3 - Article

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AN - SCOPUS:85087931939

SN - 0896-6273

VL - 107

SP - 821-835.e12

JO - Neuron

JF - Neuron

IS - 5

ER -

Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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