TMEM106B amyloid filaments in the Biondi bodies of ependymal cells
Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer's disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.
Authors
- Mehtap Bacioglu (ORCID: https://orcid.org/0000-0003-0304-7026)
- Bradley S. Glazier
- Alexey G. Murzin
- Max Jacobsen (ORCID: https://orcid.org/0000-0003-3344-898X)
- Michel Goedert (ORCID: https://orcid.org/0000-0002-5214-7886)
- Sujuan Gao (ORCID: https://orcid.org/0000-0002-6741-6380)
- Bernardino Ghetti (ORCID: https://orcid.org/0000-0002-1842-8019)
- Holly J. Garringer (ORCID: https://orcid.org/0000-0002-1899-7676)
- Rubén Vidal (ORCID: https://orcid.org/0000-0002-5803-3871)
- Sjors H. W. Scheres (ORCID: https://orcid.org/0000-0002-0462-6540)
- Kathy L. Newell (ORCID: https://orcid.org/0000-0002-1648-7357)
- Manuel Schweighauser (ORCID: https://orcid.org/0000-0002-1848-1610)
- Panagiotis Katsinelos (ORCID: https://orcid.org/0000-0001-6951-3216)
- Maria Grazia Spillantini
- Derrick Gray (ORCID: https://orcid.org/0000-0003-0593-6214)
Institutions
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- Medical Research Council (GB)
Publication Details
- Journal
- Acta Neuropathologica
- Published
- 2024-11-06
- DOI
- https://doi.org/10.1007/s00401-024-02807-w
- Citations
- 6
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- National Institute for Health and Care Research
- National Institutes of Health
- School of Medicine, Indiana University
- Medical Research Council
- NIHR Cambridge Biomedical Research Centre
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke