Skip to main content
SpringerLink
Log in

TDP-43 interacts with pathological τ protein in Alzheimer’s disease

  • Correspondence
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Amador-Ortiz C, Lin W-L, Ahmed Z, Personett D, Davies P, Duara R et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s Disease. Ann Neurol 61:435–445. https://doi.org/10.1002/ana.21154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Arai T, Mackenzie IRA, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K et al (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117:125–136. https://doi.org/10.1007/s00401-008-0480-1

    Article  CAS  PubMed  Google Scholar 

  3. Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K et al (2007) Concurrence of TDP-43, tau and α-synuclein pathology in brains of Alzheimer’s disease and dementia with Lewy bodies. Brain Res 1184:284–294. https://doi.org/10.1016/J.BRAINRES.2007.09.048

    Article  CAS  PubMed  Google Scholar 

  4. Josephs KA, Murray ME, Tosakulwong N, Weigand SD, Serie AM, Ralph PB et al (2019) Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains. Acta Neuropathol 137:227–238. https://doi.org/10.1007/s00401-018-1951-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Josephs KA, Murray ME, Whitwell JL, Tosakulwong N, Weigand SD, Petrucelli L et al (2016) Updated TDP-43 in Alzheimer’s disease staging scheme. Acta Neuropathol 131:571–585. https://doi.org/10.1007/s00401-016-1537-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M et al (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857. https://doi.org/10.1212/01.wnl.0000304041.09418.b1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Josephs KA, Whitwell JL, Tosakulwong N, Weigand SD, Murray ME, Serie AM et al (2015) TDP-43 and pathological subtype of Alzheimer’s disease impact clinical features. Ann Neurol 78:679–709. https://doi.org/10.1002/aur.1474.Replication

    Article  Google Scholar 

  8. Josephs KA, Whitwell JL, Weigand SD, Murray ME, Tosakulwong N, Liesinger AM et al (2015) TDP-43 is a key player in the clinical features associated with Alzheimer’s disease. Acta Neuropathol 127:811–824. https://doi.org/10.1007/s00401-014-1269-z.TDP-43

    Article  Google Scholar 

  9. Kadokura A, Yamazaki T, Lemere CA, Takatama M, Okamoto K (2009) Regional distribution of TDP-43 inclusions in Alzheimer disease (AD) brains: their relation to AD common pathology: original article. Neuropathology 29:566–573. https://doi.org/10.1111/j.1440-1789.2009.01017.x

    Article  PubMed  Google Scholar 

  10. Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K et al (2019) Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 142:1503–1527. https://doi.org/10.1093/brain/awz099

    Article  PubMed  PubMed Central  Google Scholar 

  11. Neumann M, Frick P, Paron F, Kosten J, Buratti E, Mackenzie IR (2020) Antibody against TDP-43 phosphorylated at serine 375 suggests conformational differences of TDP-43 aggregates among FTLD–TDP subtypes. Acta Neuropathol 140:645–658. https://doi.org/10.1007/s00401-020-02207-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nonaka T, Masuda-Suzukake M, Hasegawa M (2018) Molecular mechanisms of the co-deposition of multiple pathological proteins in neurodegenerative diseases. Neuropathology 38:64–71. https://doi.org/10.1111/neup.12427

    Article  CAS  PubMed  Google Scholar 

  13. Takeda T (2018) Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Neuropathology 38:72–81. https://doi.org/10.1111/neup.12428

    Article  CAS  PubMed  Google Scholar 

  14. Tomé SO, Vandenberghe R, Ospitalieri S, Van Schoor E, Tousseyn T, Otto M et al (2020) Distinct molecular patterns of TDP-43 pathology in Alzheimer’s disease: relationship with clinical phenotypes. Acta Neuropathol Commun 8:61. https://doi.org/10.1186/s40478-020-00934-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Simona Ospitalieri and Alicja Ronisz for all the technical support. We also thank Dr. Peter Davies, Department of Pathology, Albert Einstein College of Medicine, USA, for the gift of the PHF1 antibody.

Funding

This study was funded by the Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO G0F8516N, G065721N (DRT)), Vlaamse Impulsfinanciering voor Netwerken voor Dementieonderzoek (IWT 135043 (RV, DRT)), Alzheimer Forschung Initiative (AFI, Germany) #13803 (DRT), and Mady Browaeys Fund for Research into Frontotemporal Lobar Degeneration (RV).

Author information

Authors and Affiliations

  1. Department of Imaging and Pathology, Laboratory of Neuropathology, Leuven Brain Institute, KU-Leuven, O&N IV, Herestraat 49, box 1032, 3000, Leuven, Belgium

    Sandra O. Tomé, Luis A. Gomes, Xiaohang Li & Dietmar Rudolf Thal

  2. Department of Neurosciences, Laboratory of Cognitive Neurology, Leuven Brain Institute, KU-Leuven, Leuven, Belgium

    Rik Vandenberghe

  3. Department of Neurology, UZ Leuven, Leuven, Belgium

    Rik Vandenberghe

  4. Department of Imaging and Pathology, Translational Cell and Tissue Research Unit, KU-Leuven, Leuven, Belgium

    Thomas Tousseyn

  5. Department of Pathology, UZ Leuven, Leuven, Belgium

    Thomas Tousseyn & Dietmar Rudolf Thal

Authors
  1. Sandra O. Tomé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luis A. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rik Vandenberghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Tousseyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dietmar Rudolf Thal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dietmar Rudolf Thal.

Ethics declarations

Conflict of interest

DRT received speaker honorarium from Novartis Pharma Basel (Switzerland) and Biogen (USA), travel reimbursement from GE-Healthcare (UK), and UCB (Belgium), and collaborated with GE-Healthcare (UK), Novartis Pharma Basel (Switzerland), Probiodrug (Germany), and Janssen Pharmaceutical Companies (Belgium).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 3127 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tomé, S.O., Gomes, L.A., Li, X. et al. TDP-43 interacts with pathological τ protein in Alzheimer’s disease. Acta Neuropathol 141, 795–799 (2021). https://doi.org/10.1007/s00401-021-02295-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-021-02295-2

Search

Navigation