Brain Research

Are there sex-specific risk factors to developing brain diseases?

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Written by Ashley Curtis

There is a lot we do not know yet about brain diseases. Studying how men and women differ in the characteristics of these diseases is one way to learn more about how these diseases form, progress, and could possibly be treated. Unfortunately, research in this area is scarce, and there is a lack of knowledge on how sex might interact with disease processes.

For the past year, I’ve been a part of a large meta-analysis study with Sunnybrook, University of Toronto, and University of British Columbia researchers that looked at whether there were differences in the proportion of men and women that carried common gene mutations that are known to cause two brain disorders: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). These diseases cause behaviour and motor problems, have no known cure, and result in death in 3 to 10 years.

Genetic mutations make up about 10 per cent of ALS and 10 to 20 per cent of FTD cases. Our research study involved pooling data from 85 research articles from around the world in order to determine whether there were differences in the proportion of men and women with ALS and FTD who carried mutations in the three most common genes known to cause these disorders, called C9orf72, GRN, and MAPT.

Women more likely to carry gene mutuation related to ALS & dementia

What we found was quite surprising. Despite the well-known observation that there are more men than women with both ALS and FTD overall, we found that there are sex differences in the proportion of patients carrying certain gene mutations. In fact, we observed that women with ALS are 16 per cent more likely than men with ALS to carry C9orf72 gene mutations. We also found that women with FTD are 33 per cent more likely to carry GRN gene mutations.

Our results are surprising because due to where these mutations are located on the genes, we would expect them to be inherited similarly by men and women. So the sex differences we observed suggest that there may be sex-related factors (for example, exposure to pesticides that kill brain cells or hormonal changes) that are playing a role in how the mutations express the disease. Another possibility is that women, who live on average longer than men, are actually more likely to reach the age where the gene mutation exerts its effects, causing the symptoms of ALS and FTD to occur.

Our meta-analysis is an important first step towards further understanding the cause and progression of FTD and ALS, in which sex might play an important — and frankly overlooked — role. Examining how sex interacts with genetic causes of ALS and FTD will be important for treatment and management of the disorders.

Studying sex differences in brain disease is a small but growing research area. It will be important to continue to look at how sex plays a role not only in FTD and ALS, but also in the causes of other brain diseases, such as Parkinson’s disease, and Alzheimer’s disease. Discovery of sex differences will improve disease knowledge, and has the potential to eventually improve patient care.


Ashley Curtis is lead author of a study published in the journal Neurology.

Dr. Mary Tierney; Professor & Clinician Scientist, Department of Family & Community Medicine, University of Toronto; Director & Neuropsychologist, Primary Care Research Unit, Sunnybrook Health Sciences Centre; is senior author of the study.

About the author

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Ashley Curtis

Ashley Curtis received her PhD in Psychology (with a focus on Brain, Behaviour and Cognitive Sciences) from York University and is currently a Postdoctoral Fellow for Dr. Mary Tierney in the Evaluative Clinical Sciences platform of the Primary Care Research Unit at Sunnybrook Research Institute. She is also the Women, Gender, Sex, and Dementia Program Coordinator for the Canadian Consortium on Neurodegeneration in Aging. Her research interests include understanding how sex and gender affect the risk, cognitive outcomes, and progression of various neurodegenerative disorders, as well as investigating strategies that facilitate cognitive abilities such as attention and memory in older adults.