Summary by Natalie Pye, reviewed by Dr Ryan West and a dementia lay panel
Background:
Alzheimer’s Disease is an ageing-related disease that causes damage to nerve cells, leading to problems with movement, memory, and behaviour. The disease affects more woman than men, with evidence suggesting that treatment with oestradiol (a form of the hormone oestrogen) reduces memory loss in menopausal women.
Proteins are the building blocks of cells, each with specific functions to keep cells working properly. In Alzheimer’s Disease there is a build-up of a protein called tau which is toxic to nerve cells and leads to development of the disease. There are different forms of tau that a person can have based on their genetics, with some of these forms being more harmful and disease-causing than others.
Cells have a recycling process called autophagy which breaks down harmful debris, such as damaged proteins, and recycles them into materials the cells can use. Scientists suggest that if we can control this recycling process, it could be used to clear the build-up of tau protein, as a potential treatment for Alzheimer’s Disease.
Why is the study important?
The authors propose that oestradiol causes autophagy which promotes clearing of tau in nerve cells. The study aims to investigate how oestradiol may regulate autophagy and how this may be used as a possible strategy for treating or preventing the disease.
What did the authors do and how did they do it?
To investigate how oestradiol may cause the autophagy process to clear tau build-up, the authors used nerve like cells grown in a dish with either no tau build-up, build-up of normal tau (found in most people with Alzheimer’s disease) or build-up of a more harmful form of tau (found only in some people with Alzheimer’s disease). They applied oestradiol to the cells and measured how much autophagy occurred and how much of the tau was cleared from the cells.
What are the results?
The authors found that in cells with no tau build-up or with build-up of normal tau, applying oestradiol caused an increase in autophagy and increased the amount of tau build up cleared from the cells. However, they found that applying oestradiol to cells with the more harmful form of tau build up did not cause an increase in autophagy or an increase in the amount of tau cleared form the cell.
What do the finding mean going forward for people with the disease?
This study shows that oestradiol clears normal tau build-up in nerve like cells, suggesting that oestradiol may be a potential therapy for both men and women living with Alzheimer’s Disease. However, the study also shows that oestradiol does not work on all forms of tau, such as the more harmful form, so may not work for all people living with Alzheimer’s Disease. More research would help us understand if oestradiol can protect against Alzheimer’s Disease and if loss of oestradiol causes greater risk to women to develop the disease.
This study can be found at: https://doi.org/10.1016/j.brainres.2022.148079
Paper title: Membrane estrogen receptor ERα activation improves tau clearance via autophagy induction in a tauopathy cell model
Author list: Angelica Jardim Costa, Rafaela Brito Oliveira, Patrícia Wachilewski, Michelle Sayuri Nishino, Taysa Bervian Bassani, Roberta Sessa Stilhano, Janete Maria Cerutti, Bruno Nozima, Catarina Segreti Porto, Gustavo Jose da Silva Pereira, Ana Lopez Ramirez, Soraya Soubhi Smaili and Rodrigo Portes Ureshino