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A Common Amyloid Between Brain Diseases

This might provide extremely valuable insight into how brain disorders develop.

Common AggregateCommon Aggregate

Research funded by the National Institutes of Health and published in Cell has thoroughly described a little-known amyloid aggregate that accumulates in the brains of people suffering from multiple proteostasis-related neurological disorders.

Three classes of pathology, one protein fragment

The authors of this study list three different classes of neurodegenerative protein disorders: TDP-43 proteinopathies, such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis; tauopathies, such as Alzheimer’s disease; and synucleinopathies, such as Parkinson’s disease.

An aggregate of a single protein fragment has been found in the brains of people who had suffered from each of these different diseases. This fragment is 135 amino acids long, nearly half as long as its original protein, TMEM106B, abnormalities of which are associated with neurodegenerative disorders [1].

A protein for proteostasis

TMEM106B is found in the membranes of endosomes, which regulate protein transport within cells, and lysosomes, which are responsible for destroying unwanted proteins [2]. Other research has discovered that it is heavily involved in the functions of these organelles [3]. As these organelles maintain proteostasis in healthy cells, this leads to an unpleasant concept: one of the very proteins responsible for preventing amyloid accumulation can accumulate as an amyloid.

A large portion of this paper is given to explaining the fragment itself in exacting detail, including what it looks like under an electron microscope, what segment of the protein it is formed from (amino acids 120-254 of a protein 274 amino acids long), and the fibril aggregates that the researchers found in cells. Interestingly, Google’s AlphaFold, a powerful, AI-driven predictor of protein folding, had predicted that it would form these sorts of aggregates due to its prevalence of ß strands, which the researchers also explain in detail.

The researchers also offer evidence that TMEM106B aggregates don’t reliably show up on Western blots, a very well-known tool for protein analysis. Their findings are backed up by a recent preprint [4]. However, as the researchers note, reagents and antibodies that reliably interact with these aggregates in all their forms have not yet been developed.


This is very early, exploratory research, and this paper discusses the TMEM106B amyloid as found in post-mortem examinations rather than the brains of living people or animals. Much more research will need to be done to discover how much this fragment causes proteostasis diseases and brain deterioration, and if it does play a significant role, what approaches can be taken to destroy it or prevent its accumulation.

However, if this amyloid is found to be strongly linked to other amyloid disorders, such as Alzheimer’s and Parkinson’s, it may provide a crucial piece of the puzzle, giving researchers extremely valuable insight into methods of defeating these crippling, life-destroying, and deadly diseases.

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[1] Feng, T., Lacrampe, A., & Hu, F. (2021). Physiological and pathological functions of TMEM106B: A gene associated with brain aging and multiple brain disorders. Acta neuropathologica, 141(3), 327-339.

[2] Lang, C. M., Fellerer, K., Schwenk, B. M., Kuhn, P. H., Kremmer, E., Edbauer, D., … & Haass, C. (2012). Membrane Orientation and Subcellular Localization of Transmembrane Protein 106B (TMEM106B), a Major Risk Factor for Frontotemporal Lobar Degeneration. Journal of Biological Chemistry, 287(23), 19355-19365.

[3] Lüningschrör, P., Werner, G., Stroobants, S., Kakuta, S., Dombert, B., Sinske, D., … & Damme, M. (2020). The FTLD risk factor TMEM106B regulates the transport of lysosomes at the axon initial segment of motoneurons. Cell reports, 30(10), 3506-3519.

[4] Jiang, Y. X., Cao, Q., Sawaya, M. R., Abskharon, R., Ge, P., DeTure, M., … & Eisenberg, D. S. (2022). Amyloid fibrils in frontotemporal lobar degeneration with TDP-43 inclusions are composed of TMEM106B, rather than TDP-43. bioRxiv.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
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