Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates

Jack H. Brelstaff; Matthew Mason; Taxiarchis Katsinelos; William A. McEwan; Bernardino Ghetti; Aviva M. Tolkovsky; Maria Grazia Spillantini

doi:10.1126/sciadv.abg4980

journal article Oct 22, 2021

Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates

Jack H. Brelstaff

Matthew Mason

Taxiarchis Katsinelos

William A. McEwan Bernardino Ghetti

Aviva M. Tolkovsky

Maria Grazia Spillantini

Science Advances Vol. 7 No. 43 · American Association for the Advancement of Science (AAAS)

View at Publisher Save 10.1126/sciadv.abg4980

Abstract

Microglia change their behavior when eating live neurons containing tau protein aggregates, a hallmark of Alzheimer’s disease.

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References

61

[1]

10.1016/s1474-4422(13)70090-5

[2]

Neuropathological stageing of Alzheimer-related changes

H. Braak, E. Braak

Acta Neuropathologica 10.1007/bf00308809

[3]

10.1111/febs.14323

[4]

10.1111/jnc.14940

[5]

10.1002/glia.23475

[6]

10.15252/embj.2020105380

[7]

10.1126/science.aad8373

[8]

10.1093/brain/awz288

[9]

10.1016/j.celrep.2018.07.072

[10]

10.1002/ana.410300410

[11]

10.1016/s0002-9440(10)63421-9

[12]

10.1016/j.sbi.2020.05.011

[13]

10.1073/pnas.1301175110

[14]

Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease

Jacob W. Vogel, Yasser Iturria-Medina, Olof T. Strandberg et al.

Nature Communications 10.1038/s41467-020-15701-2

[15]

10.1093/brain/awv081

[16]

Depletion of microglia and inhibition of exosome synthesis halt tau propagation

Hirohide Asai, Seiko Ikezu, Satoshi Tsunoda et al.

Nature Neuroscience 10.1038/nn.4132

[17]

10.1523/jneurosci.4933-12.2013

[18]

10.1523/jneurosci.22-21-09340.2002

[19]

10.3389/fnins.2015.00184

[20]

10.1097/00002093-200207000-00010

[21]

10.1073/pnas.1607215114

[22]

10.1002/(sici)1097-4547(19970415)48:2<128::aid-jnr5>3.0.co;2-e

[23]

10.4103/1673-5374.165298

[24]

10.1371/journal.pone.0060921

[25]

10.1038/s41586-018-0543-y

[26]

Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease

Wolfgang J. Streit, Heiko Braak, Qing-Shan Xue et al.

Acta Neuropathologica 10.1007/s00401-009-0556-6

[27]

10.1016/j.etp.2013.04.001

[28]

STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

Damian Szklarczyk, Annika L Gable, David Lyon et al.

Nucleic Acids Research 10.1093/nar/gky1131

[29]

10.5483/bmbrep.2015.48.10.122

[30]

10.1186/1471-2474-15-93

[31]

10.1016/j.mce.2016.07.017

[32]

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

Maxim V. Kuleshov, Matthew R. Jones, Andrew D. Rouillard et al.

Nucleic Acids Research 10.1093/nar/gkw377

[33]

10.1182/blood-2002-01-0151

[34]

10.1016/j.tins.2020.10.002

[35]

10.1186/s12974-018-1309-z

[36]

10.1093/cercor/bhy152

[37]

10.1016/j.neuron.2011.11.033

[38]

10.3233/jad-150704

[39]

10.1097/nen.0000000000000030

[40]

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

Wenjie Luo, Wencheng Liu, Xiaoyan Hu et al.

Scientific Reports 10.1038/srep11161

[41]

10.1074/jbc.m111.267583

[42]

10.4049/jimmunol.1003600

[43]

10.1186/1750-1326-6-45

[44]

10.1038/srep14624

[45]

10.1016/s0197-4580(01)00311-6

[46]

10.1523/jneurosci.4403-10.2010

[47]

10.1002/glia.23782

[48]

10.1002/glia.10319

[49]

10.1016/j.neurobiolaging.2010.05.008

[50]

F. Shaerzadeh, L. Phan, D. Miller, M. Dacquel, W. Hachmeister, C. Hansen, A. Bechtle, D. Tu, M. Martcheva, T. C. Foster, A. Kumar, W. J. Streit, H. Khoshbouei, Microglia senescence occurs in both substantia nigra and ventral tegmental area. Glia 68, 2228–2245 (2020). 10.1002/glia.23834

Showing 50 of 61 references

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Details

Published: Oct 22, 2021
Vol/Issue: 7(43)

Authors

J

Jack H. Brelstaff

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.

M

Matthew Mason

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.

T

Taxiarchis Katsinelos

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.; UK Dementia Research Institute Cambridge, Island Research Building, University of Cambridge, Cambridge CB2 0AH, UK.

W

William A. McEwan

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.; UK Dementia Research Institute Cambridge, Island Research Building, University of Cambridge, Cambridge CB2 0AH, UK.

B

Bernardino Ghetti

Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.

A

Aviva M. Tolkovsky

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.

M

Maria Grazia Spillantini

Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, UK.

Cite This Article

Jack H. Brelstaff, Matthew Mason, Taxiarchis Katsinelos, et al. (2021). Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates. Science Advances, 7(43). https://doi.org/10.1126/sciadv.abg4980

Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates

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