prepared using Adobe Illustrator CS5, ImageJ/Fiji, and Microsoft Excel 2016.

**Expanded View** for this article is available online.

## Acknowledgements

The authors thank Tracy Bellande for expert technical assistance, David Cornu for expert assistance in mass spectrometry, and Clément Lena for his support. This work was supported by Grants from the Agence Nationale de la Recherche (ANR-14-CE13-0031-02 SPREADTAU), the EC Joint Programme on Neurodegenerative Diseases (JPND-NeuTARGETS-ANR-14-JPCD-0002-02; JPND-SYNACTION-ANR-15-JPWG-0012-03), the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médical, The Fondation pour la Recherche Médicale (Contract DEQ 20160334896), a "Coup d'Elan à la Recherche Francaise" award from Fondation Bettencourt-Schueler, the Fondation Simone et Cino Del Duca of the Institut de France, the Innovative Medicine Initiative 2 grant agreement No 116060 (IMPRiND, www.imprind.org) supported by the European Union's Horizon 2020 research and innovation program and EFPIA, an ERC advanced research grant (PLASLTINHIB), and the "Investissements d'Avenir" program (ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL Research University). This work benefited from the electron microscopy facility Imagerie-Gif and the proteomic facility SICaPS.

## Author contributions

RM, ANS, and AT: conceived the project, designed experiments, and wrote the manuscript. ANS, VR, LP, LBo, KM, CM-H, and AC: performed experiments. ANS, VR, and RM: analyzed data. MR: developed tools for data analysis. LBu and PH: provided tools and reagents for experiments.

## Conflict of interest

The authors declare that they have no conflict of interest.

## References

Azarias G, Kruusmägi M, Connor S, Akkuratov EE, Liu X-L, Lyons D, Brismar H, Broberger C, Aperia A (2013) A specific and essential role for Na, K-ATPase α3 in neurons co-expressing α1 and α3. *J Biol Chem* 288: 2734-2743

Bannai H, Lévi S, Schweizer C, Dahan M, Triller A (2006) Imaging the lateral diffusion of membrane molecules with quantum dots. *Nat Protoc* 1: 2628-2634

Bannai H, Lévi S, Schweizer C, Inoue T, Launey T, Racine V, Sibarita J-B, Mikoshiba K, Triller A (2009) Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics. *Neuron* 62: 670-682

Bannai H, Niwa F, Sherwood MW, Shrivastava AN, Arizono M, Miyamoto A, Sugiura K, Lévi S, Triller A, Mikoshiba K (2015) Bidirectional control of synaptic GABAAR clustering by glutamate and calcium. *Cell Rep* 13: 2768-2780

Bousset L, Pieri L, Ruiz-Arlandis G, Gath J, Jensen PH, Habenstein B, Madiona K, Oliéric V, Böckmann A, Meier BH, Melki R (2013) Structural and functional characterization of two alpha-synuclein strains. *Nat Commun* 4: 2575

Brundin P, Melki R, Kopito R (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. *Nat Rev Mol Cell Biol* 11: 301-307

Buée L, Delacourte A (1999) Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease. *Brain Pathol* 9: 681-693

Choquet D, Triller A (2013) The dynamic synapse. *Neuron* 80: 691-703

Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. *Nat Cell Biol* 11: 909-913

Compta Y, Parkkinen L, O'Sullivan SS, Vandrovcova J, Holton JL, Collins C, Lashley T, Kallis C, Williams DR, de Silva R, Lees AJ, Revesz T (2011) Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important? *Brain* 134: 1493-1505

Dujardin S, Lécolle K, Caillierez R, Bégard S, Zommer N, Lachaud C, Carrier S, Dufour N, Aurégan G, Winderickx J, Hantraye P, Déglon N, Colin M, Buée L (2014) Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. *Acta Neuropathol Commun* 2: 14

Eisenberg D, Jucker M (2012) The amyloid state of proteins in human diseases. *Cell* 148: 1188-1203

Ester M, Kriegel H-P, Sander J, Xu X (1996) A density-based algorithm for discovering clusters in large spatial databases with noise. In *KDD'96 Proceedings of the Second International Conference on Knowledge Discovery and Data Mining*, pp 226-231. Portland, Oregon

Flavin WP, Bousset L, Green ZC, Chu Y, Skarpathiotis S, Chaney MJ, Kordower JH, Melki R, Campbell EM (2017) Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins. *Acta Neuropathol* 134: 629-653

Ghee M, Melki R, Michot N, Mallet J (2005) PA700, the regulatory complex of the 26S proteasome, interferes with alpha-synuclein assembly. *FEBS J* 272: 4023-4033

Goedert M, Eisenberg DS, Crowther RA (2017) Propagation of Tau aggregates and neurodegeneration. *Annu Rev Neurosci* 40: 189-210

Goniotaki D, Lakkaraju AKK, Shrivastava AN, Bakirci P, Sorce S, Senatore A, Marpakwar R, Hornemann S, Gasparini F, Triller A, Aguzzi A (2017) Inhibition of group-I metabotropic glutamate receptors protects against prion toxicity. *PLoS Pathog* 13: e1006733

Greger IH, Watson JF, Cull-Candy SG (2017) Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins. *Neuron* 94: 713-730

Guo JL, Narasimhan S, Changolkar L, He Z, Stieber A, Zhang B, Gathagan RJ, Iba M, McBride JD, Trojanowski JQ, Lee VMY (2016) Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice. *J Exp Med* 213: 2635-2654

Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, Ouidja MO, Brodsky FM, Marasa J, Bagchi DP, Kotzbauer PT, Miller TM, Papy-Garcia D, Diamond MI (2013) Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. *Proc Natl Acad Sci USA* 110: E3138-E3147

Howlett DR, Whitfield D, Johnson M, Attems J, O'Brien JT, Aarsland D, Lai MKP, Lee JH, Chen C, Ballard C, Hortobágyi T, Francis PT (2015) Regional multiple pathology scores are associated with cognitive decline in lewy body dementias. *Brain Pathol* 25: 401-408

Hüls S, Högen T, Vassallo N, Danzer KM, Hengerer B, Giese A, Herms J (2011) AMPA-receptor-mediated excitatory synaptic transmission is enhanced by iron-induced α-synuclein oligomers. *J Neurochem* 117: 868-878

Iba M, McBride JD, Guo JL, Zhang B, Trojanowski JQ, Lee VM-Y (2015) Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC's afferent and efferent connections. *Acta Neuropathol* 130: 349-362

Irwin DJ, Lee VM-Y, Trojanowski JQ (2013) Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. *Nat Rev Neurosci* 14: 626-636
prepared using Adobe Illustrator CS5, ImageJ/Fiji, and Microsoft Excel 2016.

**Expanded View** for this article is available online.

## Acknowledgements

The authors thank Tracy Bellande for expert technical assistance, David Cornu for expert assistance in mass spectrometry, and Clément Lena for his support. This work was supported by Grants from the Agence Nationale de la Recherche (ANR-14-CE13-0031-02 SPREADTAU), the EC Joint Programme on Neurodegenerative Diseases (JPND-NeuTARGETS-ANR-14-JPCD-0002-02; JPND-SYNACTION-ANR-15-JPWG-0012-03), the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médical, The Fondation pour la Recherche Médicale (Contract DEQ 20160334896), a "Coup d'Elan à la Recherche Francaise" award from Fondation Bettencourt-Schueler, the Fondation Simone et Cino Del Duca of the Institut de France, the Innovative Medicine Initiative 2 grant agreement No 116060 (IMPRiND, www.imprind.org) supported by the European Union's Horizon 2020 research and innovation program and EFPIA, an ERC advanced research grant (PLASLTINHIB), and the "Investissements d'Avenir" program (ANR-10-LABX-54 MEMO LIFE and ANR-11-IDEX-0001-02 PSL Research University). This work benefited from the electron microscopy facility Imagerie-Gif and the proteomic facility SICaPS.

## Author contributions

RM, ANS, and AT: conceived the project, designed experiments, and wrote the manuscript. ANS, VR, LP, LBo, KM, CM-H, and AC: performed experiments. ANS, VR, and RM: analyzed data. MR: developed tools for data analysis. LBu and PH: provided tools and reagents for experiments.

## Conflict of interest

The authors declare that they have no conflict of interest.

## References

Azarias G, Kruusmägi M, Connor S, Akkuratov EE, Liu X-L, Lyons D, Brismar H, Broberger C, Aperia A (2013) A specific and essential role for Na, K-ATPase α3 in neurons co-expressing α1 and α3. *J Biol Chem* 288: 2734-2743

Bannai H, Lévi S, Schweizer C, Dahan M, Triller A (2006) Imaging the lateral diffusion of membrane molecules with quantum dots. *Nat Protoc* 1: 2628-2634

Bannai H, Lévi S, Schweizer C, Inoue T, Launey T, Racine V, Sibarita J-B, Mikoshiba K, Triller A (2009) Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics. *Neuron* 62: 670-682

Bannai H, Niwa F, Sherwood MW, Shrivastava AN, Arizono M, Miyamoto A, Sugiura K, Lévi S, Triller A, Mikoshiba K (2015) Bidirectional control of synaptic GABAAR clustering by glutamate and calcium. *Cell Rep* 13: 2768-2780

Bousset L, Pieri L, Ruiz-Arlandis G, Gath J, Jensen PH, Habenstein B, Madiona K, Oliéric V, Böckmann A, Meier BH, Melki R (2013) Structural and functional characterization of two alpha-synuclein strains. *Nat Commun* 4: 2575

Brundin P, Melki R, Kopito R (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. *Nat Rev Mol Cell Biol* 11: 301-307

Buée L, Delacourte A (1999) Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease. *Brain Pathol* 9: 681-693

Choquet D, Triller A (2013) The dynamic synapse. *Neuron* 80: 691-703

Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M (2009) Transmission and spreading of tauopathy in transgenic mouse brain. *Nat Cell Biol* 11: 909-913

Compta Y, Parkkinen L, O'Sullivan SS, Vandrovcova J, Holton JL, Collins C, Lashley T, Kallis C, Williams DR, de Silva R, Lees AJ, Revesz T (2011) Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important? *Brain* 134: 1493-1505

Dujardin S, Lécolle K, Caillierez R, Bégard S, Zommer N, Lachaud C, Carrier S, Dufour N, Aurégan G, Winderickx J, Hantraye P, Déglon N, Colin M, Buée L (2014) Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. *Acta Neuropathol Commun* 2: 14

Eisenberg D, Jucker M (2012) The amyloid state of proteins in human diseases. *Cell* 148: 1188-1203

Ester M, Kriegel H-P, Sander J, Xu X (1996) A density-based algorithm for discovering clusters in large spatial databases with noise. In *KDD'96 Proceedings of the Second International Conference on Knowledge Discovery and Data Mining*, pp 226-231. Portland, Oregon

Flavin WP, Bousset L, Green ZC, Chu Y, Skarpathiotis S, Chaney MJ, Kordower JH, Melki R, Campbell EM (2017) Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins. *Acta Neuropathol* 134: 629-653

Ghee M, Melki R, Michot N, Mallet J (2005) PA700, the regulatory complex of the 26S proteasome, interferes with alpha-synuclein assembly. *FEBS J* 272: 4023-4033

Goedert M, Eisenberg DS, Crowther RA (2017) Propagation of Tau aggregates and neurodegeneration. *Annu Rev Neurosci* 40: 189-210

Goniotaki D, Lakkaraju AKK, Shrivastava AN, Bakirci P, Sorce S, Senatore A, Marpakwar R, Hornemann S, Gasparini F, Triller A, Aguzzi A (2017) Inhibition of group-I metabotropic glutamate receptors protects against prion toxicity. *PLoS Pathog* 13: e1006733

Greger IH, Watson JF, Cull-Candy SG (2017) Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins. *Neuron* 94: 713-730

Guo JL, Narasimhan S, Changolkar L, He Z, Stieber A, Zhang B, Gathagan RJ, Iba M, McBride JD, Trojanowski JQ, Lee VMY (2016) Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice. *J Exp Med* 213: 2635-2654

Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, Ouidja MO, Brodsky FM, Marasa J, Bagchi DP, Kotzbauer PT, Miller TM, Papy-Garcia D, Diamond MI (2013) Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. *Proc Natl Acad Sci USA* 110: E3138-E3147

Howlett DR, Whitfield D, Johnson M, Attems J, O'Brien JT, Aarsland D, Lai MKP, Lee JH, Chen C, Ballard C, Hortobágyi T, Francis PT (2015) Regional multiple pathology scores are associated with cognitive decline in lewy body dementias. *Brain Pathol* 25: 401-408

Hüls S, Högen T, Vassallo N, Danzer KM, Hengerer B, Giese A, Herms J (2011) AMPA-receptor-mediated excitatory synaptic transmission is enhanced by iron-induced α-synuclein oligomers. *J Neurochem* 117: 868-878

Iba M, McBride JD, Guo JL, Zhang B, Trojanowski JQ, Lee VM-Y (2015) Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC's afferent and efferent connections. *Acta Neuropathol* 130: 349-362

Irwin DJ, Lee VM-Y, Trojanowski JQ (2013) Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. *Nat Rev Neurosci* 14: 626-636
Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX, Lee EB, Van Deerlin VM, Lopez OL, Kofler JK, Nelson PT, Jicha GA, Woltjer R, Quinn JF, Kaye J, Leverenz JB, Tsuang D, Longfellow K, Yearout D, Kukull W *et al* (2017) Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. *Lancet Neurol* 16: 55–65

Ivenshitz M, Segal M (2010) Neuronal density determines network connectivity and spontaneous activity in cultured hippocampus. *J Neurophysiol* 104: 1052–1060

Izeddin I, Boulanger J, Racine V, Specht CG, Kechkar A, Nair D, Triller A, Choquet D, Dahan M, Sibarita JB (2012) Wavelet analysis for single molecule localization microscopy. *Opt Express* 20: 2081–2095

Jellinger KA (2012) Interaction between pathogenic proteins in neurodegenerative disorders. *J Cell Mol Med* 16: 1166–1183

Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J, Sharma AM, Miller TM, Diamond MI (2016) Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. *Neuron* 92: 796–812

Kopec CD, Li B, Wei W, Boehm J, Malinow R (2006) Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. *J Neurosci* 26: 2000–2009

Kovacs GG (2015) Neuropathology of tauopathies: principles and practice. *Neuropathol Appl Neurobiol* 41: 3–23

Labbadia J, Morimoto RI (2015) The biology of proteostasis in aging and disease. *Annu Rev Biochem* 84: 435–464

Lévi S, Schweizer C, Bannai H, Pascual O, Charrier C, Triller A (2008) Homeostatic regulation of synaptic GlyR numbers driven by lateral diffusion. *Neuron* 59: 261–273

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Malkusch S, Heilemann M (2016) Extracting quantitative information from single-molecule super-resolution imaging data with LAMA – Localization Microscopy Analyzer. *Sci Rep* 6: 34486

Melki R (2017) The multitude of therapeutic targets in neurodegenerative proteinopathies. In *Disease-modifying targets in neurodegenerative disorders*, Baekelandt V, Lobbestael E (eds), pp 1–20. London: Academic Press

Meyer N, Richter N, Fan Z, Siemonsmeier G, Pivneva T, Jordan P, Steinhäuser C, Semtner M, Nolte C, Kettenmann H (2018) Oligodendrocytes in the mouse corpus callosum maintain axonal function by delivery of glucose. *Cell Rep* 22: 2383–2394

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Narasimhan S, Guo JL, Changolkar L, Stieber A, McBride JD, Silva LV, He Z, Zhang B, Gathagan RJ, Trojanowski JQ, Lee VMY (2017) Pathological tau strains from human brains recapitulate the diversity of tauopathies in non-transgenic mouse brain. *J Neurosci* 37: 11406–11423

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Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX, Lee EB, Van Deerlin VM, Lopez OL, Kofler JK, Nelson PT, Jicha GA, Woltjer R, Quinn JF, Kaye J, Leverenz JB, Tsuang D, Longfellow K, Yearout D, Kukull W et al (2017) Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. *Lancet Neurol* 16: 55–65

Ivenshitz M, Segal M (2010) Neuronal density determines network connectivity and spontaneous activity in cultured hippocampus. *J Neurophysiol* 104: 1052–1060

Izeddin I, Boulanger J, Racine V, Specht CG, Kechkar A, Nair D, Triller A, Choquet D, Dahan M, Sibarita JB (2012) Wavelet analysis for single molecule localization microscopy. *Opt Express* 20: 2081–2095

Jellinger KA (2012) Interaction between pathogenic proteins in neurodegenerative disorders. *J Cell Mol Med* 16: 1166–1183

Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J, Sharma AM, Miller TM, Diamond MI (2016) Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. *Neuron* 92: 796–812

Kopec CD, Li B, Wei W, Boehm J, Malinow R (2006) Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. *J Neurosci* 26: 2000–2009

Kovacs GG (2015) Neuropathology of tauopathies: principles and practice. *Neuropathol Appl Neurobiol* 41: 3–23

Labbadia J, Morimoto RI (2015) The biology of proteostasis in aging and disease. *Annu Rev Biochem* 84: 435–464

Lévi S, Schweizer C, Bannai H, Pascual O, Charrier C, Triller A (2008) Homeostatic regulation of synaptic GlyR numbers driven by lateral diffusion. *Neuron* 59: 261–273

Liu H, Sadygov RG, Yates JR 3rd (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. *Anal Chem* 76: 4193–4201

Loh KH, Stawski PS, Draycott AS, Udeshi ND, Lehrman EK, Wilton DK, Svinkina T, Deerinck TJ, Ellisman MH, Stevens B, Carr SA, Ting AY (2016) Proteomic analysis of unbounded cellular compartments: synaptic clefts. *Cell* 166: 1295–1307 e21

Malkusch S, Endesfelder U, Mondry J, Gelléri M, Verveer PJ, Heilemann M (2012) Coordinate-based colocalization analysis of single-molecule localization microscopy data. *Histochem Cell Biol* 137: 1–10

Malkusch S, Heilemann M (2016) Extracting quantitative information from single-molecule super-resolution imaging data with LAMA – Localization Microscopy Analyzer. *Sci Rep* 6: 34486

Melki R (2017) The multitude of therapeutic targets in neurodegenerative proteinopathies. In *Disease-modifying targets in neurodegenerative disorders*, Baekelandt V, Lobbestael E (eds), pp 1–20. London: Academic Press

Meyer N, Richter N, Fan Z, Siemonsmeier G, Pivneva T, Jordan P, Steinhäuser C, Semtner M, Nolte C, Kettenmann H (2018) Oligodendrocytes in the mouse corpus callosum maintain axonal function by delivery of glucose. *Cell Rep* 22: 2383–2394

Morales R, Moreno-Gonzalez I, Soto C (2013) Cross-seeding of misfolded proteins: implications for etiology and pathogenesis of protein misfolding diseases. *PLoS Pathog* 9: 1–4

Moussaud S, Jones DR, Moussaud-Lamodière EL, Delenclos M, Ross OA, McLean PJ (2014) Alpha-synuclein and tau: teammates in neurodegeneration? *Mol Neurodegener* 9: 43

Narasimhan S, Guo JL, Changolkar L, Stieber A, McBride JD, Silva LV, He Z, Zhang B, Gathagan RJ, Trojanowski JQ, Lee VMY (2017) Pathological tau strains from human brains recapitulate the diversity of tauopathies in non-transgenic mouse brain. *J Neurosci* 37: 11406–11423

Nesvizhskii AI, Keller A, Kolker E, Aebersold R (2003) A statistical model for identifying proteins by tandem mass spectrometry. *Anal Chem* 75: 4646–4658

Ohnishi T, Yanazawa M, Sasahara T, Kitamura Y, Hiroaki H, Fukazawa Y, Kii I, Nishiyama T, Kakita A, Takeda H, Takeuchi A, Arai Y, Ito A, Komura H, Hirao H, Satomura K, Inoue M, Muramatsu S-I, Matsui K, Tada M et al (2015) Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly. *Proc Natl Acad Sci USA* 112: E4465–E4474

Persson F, Lindén M, Unoson C, Elf J (2013) Extracting intracellular diffusive states and transition rates from single-molecule tracking data. *Nat Methods* 10: 265–269

Pooler AM, Phillips EC, Lau DHW, Noble W, Hanger DP (2013) Physiological release of endogenous tau is stimulated by neuronal activity. *EMBO Rep* 14: 389–394

Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, Triller A (2010) Deleterious effects of amyloid β oligomers acting as an extracellular scaffold for mGluR5. *Neuron* 66: 739–754

Rosen GD, La Porte NT, Diechtiareff B, Pung CJ, Nissanov J, Gustafson C, Bertrand L, Gefen S, Fan Y, Tretiak OJ, Manly KF, Park MR, Williams AG, Connolly MT, Capra JA, Williams RW (2003) Informatics center for mouse genomics: the dissection of complex traits of the nervous system. *Neuroinformatics* 1: 327–342

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<figure><img src="image_26.png" /></figure>

**License:** This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. *Bioinformatics* 27: 431–432

Strowbridge BW (1999) Glutamate receptors mediate TTX-resistant synchronous activity in the rat hippocampus. *J Neurosci* 19: 5758–5767

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein-protein interaction networks, integrated over the tree of life. *Nucleic Acids Res* 43: D447–D452

Tagawa A, Mezzacasa A, Hayer A, Longatti A, Pelkmans L, Helenius A (2005) Assembly and trafficking of caveolar domains in the cell. *J Cell Biol* 170: 769–779

Takeda S, Wegmann S, Cho H, DeVos SL, Commins C, Roe AD, Nicholls SB, Carlson GA, Pitstick R, Nobuhara CK, Costantino I, Frosch MP, Müller DJ, Irimia D, Hyman BT (2015) Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain. *Nat Commun* 6: 8490

Tardivel M, Bégard S, Bousset L, Dujardin S, Coens A, Melki R, Buée L, Colin M (2016) Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies. *Acta Neuropathol Commun* 4: 117

Triller A, Choquet D (2008) New concepts in synaptic biology derived from single-molecule imaging. *Neuron* 59: 359–374

Vizcaíno JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Ríos D, Dianes JA, Sun Z, Farrah T, Bandeira N, Binz P-A, Xenarios I, Eisenacher M, Mayer G,

Gatto L, Campos A, Chalkley RJ, Kraus H-J, Albar JP, Martinez-Bartolomé S et al (2014) ProteomeXchange provides globally coordinated proteomics data submission and dissemination. *Nat Biotechnol* 32: 223–226

Walsh DM, Thulin E, Minogue AM, Gustavsson N, Pang E, Teplow DB, Linse S (2009) A facile method for expression and purification of the Alzheimer's disease-associated amyloid beta-peptide. *FEBS J* 276: 1266–1281

Wegmann S, Nicholls S, Takeda S, Fan Z, Hyman BT (2016) Formation, release, and internalization of stable tau oligomers in cells. *J Neurochem* 121: 715–725

Woerman AL, Aoyagi A, Patel S, Kazmi SA, Lobach I, Grinberg LT, McKee AC, Seeley WW, Olson SH, Prusiner SB (2016) Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells. *Proc Natl Acad Sci USA* 113: E8187–E8196

Zhao WQ, Santini F, Breese R, Ross D, Zhang XD, Stone DJ, Ferrer M, Townsend M, Wolfe AL, Seager MA, Kinney GG, Shughrue PJ, Ray WJ (2010) Inhibition of calcineurin-mediated endocytosis and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid β oligomer-induced synaptic disruption. *J Biol Chem* 285: 7619–7632

<figure><img src="image_27.png" /></figure>

**License:** This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.