A recent study from the Mayo Clinic, published in JAMA Network Open, found that women with both Alzheimer's-related brain changes and abnormal levels of alpha-synuclein—a protein linked to Parkinson's disease—experienced a much faster progression of Alzheimer's disease compared to men. The research indicated that tau protein buildup, which is characteristic of Alzheimer's, advanced up to 20 times more quickly in these women.
Alpha-synuclein is commonly associated with Lewy body diseases such as Parkinson's disease and dementia with Lewy bodies. Both tau and alpha-synuclein are naturally present in the brain but can form abnormal clumps in neurodegenerative diseases. These deposits disrupt communication between brain cells and contribute to cognitive decline.
The study analyzed data from 415 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative, a national consortium tracking brain changes over time. Participants underwent cerebrospinal fluid testing for abnormal alpha-synuclein and repeated imaging to monitor tau accumulation. About 17% of those studied showed evidence of abnormal alpha-synuclein.
Researchers observed that among participants with both types of protein abnormalities, women accumulated tau at a much higher rate than men who had similar coexisting protein changes. This difference was not seen in male participants.
"This opens an entirely new direction for understanding why women bear a disproportionate burden of dementia," said Elijah Mak, Ph.D., first author of the study and a Mayo Clinic neuroimaging researcher. "If we can unravel the mechanisms behind this vulnerability, we may uncover targets we haven't considered before."
Kejal Kantarci, M.D., senior author and Mayo Clinic neuroradiologist, led the team using advanced imaging techniques to track Alzheimer’s progression.
The findings may help explain why nearly two-thirds of people living with Alzheimer's disease in the United States are women. Researchers are now investigating whether similar sex-specific effects appear in patients with dementia with Lewy bodies, where alpha-synuclein is the main pathological driver rather than a secondary factor. This ongoing work aims to determine if the observed differences are unique to Alzheimer’s or reflect broader vulnerabilities across neurodegenerative diseases.
