The answer to why women are almost twice as likely as men to develop late-onset Alzheimer’s disease may lie in hormones.

With the help of federal funding, Rebecca MacPherson (PhD ’14) and her research team at Brock University are aiming to learn more about the link between the disease and a drop in estrogen in women.

“Being a female is the second-greatest risk factor for late-onset Alzheimer’s disease,” says the Associate Professor of Health Sciences. “Most Alzheimer’s disease research focuses on males, so we don’t fully understand why females are at greater risk.”

MacPherson and her team have made great strides in linking a protein called brain derived neurotrophic factor (BDNF) to a biomarker in the brain that is related to Alzheimer’s disease.

BDNF levels are lower in patients with Alzheimer’s — and also, in post-menopausal women, says MacPherson.

To test out the association between estrogen loss and late-onset Alzheimer’s disease, MacPherson and her team have received a $130,000 Biomedical Discovery Grant from the Canadian Institutes of Health Research (CIHR).

BDNF — which MacPherson calls “brain fertilizer,” because it helps maintain healthy brain cells, as well as grow new ones — can reduce the production of small proteins called beta-amyloid.

Beta-amyloid clumps together and forms plaques in the brains of people living with Alzheimer’s disease. These plaques damage the brain by blocking cell-signalling processes, among other effects.

The female hormone estrogen regulates BDNF levels, says MacPherson. But estrogen levels drop dramatically during the progression to menopause.

MacPherson and her team will study if and how targeting BDNF signalling in post-menopausal females will prevent the production of beta-amyloid that lead to Alzheimer’s disease, and in the process, improve memory and maintain brain health.

She says one of the easiest ways to increase BDNF is through physical exercise.

“But for those who have physical or other limitations, it will be important to identify other methods that complement the benefits of exercise,” she says.

“The majority of exercise-related research and recommendations are based on data collected from male participants,” says MacPherson. “However, males and females may respond differently to the same exercise or therapy, therefore, research should focus on alternative therapies that can reduce the detrimental effects of menopause.”

The team will also study post-mortem human brain samples from male and female patients diagnosed with and without Alzheimer’s to further explore the differences in male and female brains.

In addition to the greater risk of Alzheimer’s disease with the onset of menopause in females, the risk for other health conditions is also increased. One example is sarcopenia, an age-associated disease characterized by muscle wasting and weakness.

“Interestingly, muscle can also regulate BDNF content in the brain,” says MacPherson, adding that part of the research will examine how menopause impacts muscle health, and how targeting muscle health in turn affects brain health.

Working on this with MacPherson is Val Fajardo (BSc ’09, MSc ’12), Associate Professor of Kinesiology and Canada Research Chair in Tissue Re-modelling and Plasticity Throughout the Lifespan.

Other team members that contributed to the grant include Kinesiology master’s student Bianca Marcella and Health Sciences master’s student Ahmad Mohammad.

CIHR’s Biomedical Discovery Grant is a one-year, special opportunity under the National Women’s Health Research Initiative co-led by CIHR. The initiative aims to advance a co-ordinated research program that addresses under-researched and high-priority areas of women’s health.