- In a study of older adults with Alzheimer’s, researchers examined biological sex and disease progression in relation to a protein related to Parkinson’s disease.
- The protein, called alpha-synuclein, can also occur at abnormal levels in people with Alzheimer’s, even though they do not have Parkinson’s.
- The study results indicated that women who tested positive for alpha-synuclein showed a much faster buildup of the protein that drives Alzheimer’s progression compared to men.
Alzheimer’s disease affects more than 7 million older adults in the United States as of 2025, and scientists
The disease affects women at a higher rate than men, and women also tend to experience a faster rate of cognitive decline.
A new study from the Mayo Clinic took a closer look at Alzheimer’s, biological sex, and the alpha-synuclein protein in relation to disease progression.
Alzheimer’s disease is a brain disorder that gets worse over time. It affects memory, thinking, and daily functioning.
Parkinson’s disease is also a progressive neurological condition that causes movement symptoms such as tremors and stiffness. Like Alzheimer’s, it has no cure, but medications can help manage symptoms.
Although the two conditions are distinct, they share some biological similarities. Both are linked to abnormal protein buildup in the brain through the tau protein in Alzheimer’s disease and abnormal alpha-synuclein in Parkinson’s disease.
Because of their similarities, researchers wanted to explore whether the Parkinson’s protein might also play a role in Alzheimer’s disease progression. They analyzed data from 415 participants in the Alzheimer’s Disease Neuroimaging Initiative.
The participants ranged from cognitively healthy adults to people with mild cognitive impairment or dementia. The researchers used cerebrospinal fluid testing and brain scans to measure levels of alpha-synuclein and tau.
The researchers analyzed data collected between 2015 and 2023 with participants having a median follow-up of about 1.23 years.
Overall, about 21.5% of men tested positive for misfolded alpha-synuclein compared with around 12% of women.
Despite the higher positivity rate among men, the protein appeared to have a much stronger impact in women.
Women who tested positive for alpha-synuclein accumulated tau at a much faster rate over time, with buildup occurring about 20 times faster than in men with the same abnormal protein levels.
The findings suggest alpha-synuclein may act as an Alzheimer’s disease accelerator in women. The researchers say this could help explain why women account for nearly two-thirds of Alzheimer’s disease cases in the U.S.
The study’s first author, Elijah Mak, PhD, spoke with Medical News Today about the findings and said they “suggest that biological sex should be considered importantly in how we interpret findings in dementia research.”
Mak noted that the sample size of alpha-synuclein-positive women was “relatively small” and that further research is needed.
In terms of affecting future clinical practice, if these results are replicated, Mak said the findings suggest people who have both Alzheimer’s-related brain changes and abnormal alpha-synuclein could potentially benefit from therapies that target both disease pathways.
Christina Ni, MD, board-certified psychiatrist and Interventional Medical Director with Mindpath Health, who was not involved in the study, shared her thoughts with MNT.
“This is a meaningful finding,” said Ni, “[the study] shows that Alzheimer’s pathology does not progress uniformly across sexes when additional brain protein abnormalities are present.”
Ni said that while they have long known about the disparity between women and men, the findings affect how that disparity is viewed.
“That shifts the conversation from ‘women are more affected’ to ‘women may have biologically distinct disease trajectories,’” explained Ni. “This moves the observation from a population statistic to a more biologically meaningful understanding of how the disease progresses.”
Does this mean women need different treatment?
Daniel Truong, MD, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center and editor in chief of the Journal of Clinical Parkinsonism and Related Disorders, who was also not involved in the study, also spoke with MNT about the study findings.
“In the broader landscape of Alzheimer’s research, this finding is scientifically important but not yet field-defining. Its significance lies in three specific areas: understanding mixed pathology, sex differences, and biomarker-guided trials.”
— Daniel Truong, MD
Truong said the study “refines” how Alzheimer’s is viewed in women instead of being a “wholesale rewrite.” Instead of chalking up Alzheimer’s progression to merely progressing faster in women, Truong said it shows that “some women have a specific accelerator.”
Ni noted that, presently, men and women are approached with similar treatment options for Alzheimer’s, but this study could eventually impact this approach.
“It’s important to remember that behind every data point surrounding Alzheimer’s disease is a patient and their loved ones. Advancing research that helps us better understand and navigate treatment is critical both for improving brain health, but also for easing the enormous human and caregiving burden Alzheimer’s disease places on patients and their families.”
— Christina Ni, MD
While Truong said the study will not presently change treatments, it has the potential to.
“The study does not mean men and women with Alzheimer’s should be treated differently today, but it suggests that future treatment strategies may need to consider sex and co-existing protein pathologies when tailoring therapy,” explained Truong.
