Alzheimer’s: Women Show Faster Decline Due to Alpha-Synuclein, Study Finds
New research suggests a potential explanation for why Alzheimer’s disease often progresses more rapidly in women than in men. A study published in JAMA Network Open has found that the presence of a protein typically associated with Parkinson’s disease, alpha-synuclein, significantly accelerates brain changes in women already exhibiting signs of Alzheimer’s pathology.
Alzheimer’s disease is characterized by the buildup of tau protein in the brain, disrupting communication between brain cells and leading to cognitive decline. However, some individuals with Alzheimer’s also exhibit abnormal clumps of alpha-synuclein, a protein primarily linked to Parkinson’s disease. The Mayo Clinic study investigated the interplay between these two proteins and its impact on disease progression.
Researchers analyzed data from 415 participants with Alzheimer’s disease, tracking brain changes over time using cerebrospinal fluid testing to detect alpha-synuclein and brain imaging to measure tau accumulation. The findings revealed a striking difference: among patients with both tau and alpha-synuclein abnormalities, brain changes occurred up to 20 times faster in women compared to men.
“When we see disease-related changes unfolding at dramatically different rates, we cannot keep approaching Alzheimer’s as though it behaves exactly the same way in everyone,” said Dr. Kejal Kantarci, senior author of the study, in a statement. This suggests that alpha-synuclein may play a more significant role in accelerating dementia progression in women.
Approximately 17% of the study participants showed evidence of abnormal alpha-synuclein. The research team emphasizes that this discovery highlights the importance of recognizing sex-specific differences in Alzheimer’s disease. “Recognizing these sex-specific differences could help us design more targeted clinical trials and ultimately more personalized treatment strategies,” Dr. Kantarci explained.
The study’s lead author, Dr. Elijah Mak, added, “This opens an entirely new direction for understanding why women bear a disproportionate burden of dementia. If People can unravel the mechanisms behind this vulnerability, we may uncover targets we haven’t considered before.” Women currently account for nearly two-thirds of Alzheimer’s patients, and this research offers a potential clue as to why.
The findings suggest that the interaction between tau and alpha-synuclein creates a unique vulnerability in the female brain. While alpha-synuclein often appears as a “silent passenger” in Alzheimer’s patients, its presence appears to significantly worsen the prognosis for women. This doesn’t mean that alpha-synuclein is a primary driver of Alzheimer’s, but rather that its co-occurrence with tau pathology has a particularly detrimental effect in women.
This research underscores the need for a more nuanced understanding of Alzheimer’s disease, moving away from a “one-size-fits-all” approach to diagnosis, and treatment. The study suggests that women may benefit from different screening protocols to accurately assess their risk and predict disease trajectory, potentially including evaluation for Lewy Body proteins.
In related news, an experimental drug, zorevunersen, developed by Stoke Therapeutics and Biogen, is showing promise in treating Dravet syndrome, a rare and severe form of childhood epilepsy. Early and mid-stage trials reported in The New England Journal of Medicine demonstrated that zorevunersen, administered via injection into the cerebrospinal fluid, significantly reduced seizure frequency in children and teenagers with Dravet syndrome. Patients receiving the drug experienced up to a 91% reduction in seizures, with monthly episode counts decreasing from an average of 17 to between 1.5 and 7, depending on the dosage.
Dravet syndrome, affecting approximately 1 in 15,000 children, is caused by a genetic mutation that impairs nerve cell function. Zorevunersen works by increasing the production of protein from the patient’s healthy copy of the gene. The drug was generally well-tolerated, with most side effects being mild to moderate. Larger trials are currently underway to further evaluate its efficacy and safety.
Helen Cross, a study leader from University College London, stated, “I regularly see patients with hard-to-treat genetic epilepsies with impacts that go beyond seizures and it’s heartbreaking when treatment options are limited.” The mother of an 8-year-old participant in the trial shared that the drug “has completely changed our lives,” allowing her son to experience a quality of life previously unimaginable.