Accumulation of protein aggregates in the brain is a hallmark of several neurodegenerative diseases. In Alzheimer's disease (AD), clumps of amyloid-beta and tangled tau proteins build up in regions of the brain that help to control memory. In back-to-back studies recently published in the Nature journal, researchers identify a novel protein aggregate in aging brains, composed of fibrils of a protein called TMEM106b. In separate articles published in the same issue of Nature, two teams of researchers led by David Eisenberg at UCLA (USA), Sjors Scheres and Michel Goedert at the University of Cambridge (UK) use similar cryo-electron microscopy techniques to probe the composition of protein aggregates from the brains of people of different ages, and with different types of neurodegenerative diseases. Studying samples donated by people who died of frontotemporal lobar degeneration, David Eisenberg and colleagues found filaments of TMEM106b, which has known genetic ties to frontotemporal dementia (FTD).
Similarly, the Cambridge team identified TMEM106b aggregates in brain samples from 22 people with different types of neurodegenerative disease, including FTD, familial AD, dementia with Lewy bodies and multiple system atrophy. Both research teams observed a range of different TMEM106b structures and folds, adopting different shapes in the brain, although no clear pattern or association between types of structure and disease was observed. Sjors Scheres and Michel Goedert also found that TMEM106b aggregates were much more prevalent in the brains of older individuals aged over 70 years, suggesting that accumulation of this protein aggregate may be age-dependent. Further research is required to understand the pathological significance of these aggregates, and how they are linked to the genetic mutations in TMEM106b that are found in dementias such as FTD.