October 29, 2021

expert reaction to study looking at tau accumulation in Alzheimer’s disease

A study published in Science Advances looks at tau seed accumulation in Alzheimer’s disease.

Prof Tara Spires-Jones, UK Dementia Research Institute Group Leader, and Deputy Director of the Centre for Discovery Brain Sciences, University of Edinburgh, said:

“Meisl and colleagues used mathematical modelling based on several studies examining tau pathology in the brains of people with Alzheimer’s disease to estimate how this pathological protein propagates through the brain.  The model indicates that after an early initial spread of tau between different brain areas, the spread from place to place no longer drives the pathology, rather local replication of the tau takes over as the dominant factor in tau accumulation.  The authors estimate that the amount of tau “seeds” that are being copied in the brain doubles around every 5 years, reinforcing the well-accepted idea that there is a very long silent phase of Alzheimer’s disease when pathology is building up in the brain before any symptoms appear.  This work is important because we know that wherever tau pathology goes in the brain, cells die.  Understanding tau propagation is important for developing future treatments for Alzheimer’s.”

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said:

“Tau is a protein that forms tangles inside brain nerve cells during Alzheimer’s but exactly how the protein spreads throughout the human brain during the disease has so far eluded scientists.  Alzheimer’s disease is the leading cause of dementia, a devastating condition that affects the lives of nearly one million people in the UK.

“In this work, scientists have used a multi-angled approach to shed more light on the mechanisms by which tau contributes to the progression of Alzheimer’s disease.  This study highlights that the replication of tau is the limiting factor in the progression of mid-to-late stages of Alzheimer’s disease rather than the spread of tau between brain regions.  The findings could help scientists focus in on the most effective way to target potential new treatments for Alzheimer’s disease.

“This thorough research study highlights the advantage of bringing together different disciplines and datasets to advance our understanding of Alzheimer’s disease, including postmortem brain tissue and PET brain imaging.

“Tau is a culprit protein in a number of different dementias, and it would make sense to explore how this protein spreads in diseases like frontotemporal dementia.  Hopefully this study and others like it will help focus the development of future treatments that target tau, so any future treatments have a better chance of slowing the disease processes themselves and have benefit for people with dementia.”

‘In vivo rate-determining steps of tau seed accumulation in Alzheimer’s disease’ by Georg Meisl et al. was published in Science Advances at 19:00 UK time on Friday 29 October 2021t.

DOI: 10.1126/sciadv.abh1448

Declared interests

Prof Tara Spires-Jones: “I have no conflicts with this study.”

Dr Sara Imarisio: “No conflicts but Prof Rowe who is ARUKs Chief scientific officer is author on this paper.”