Study finds more Alzheimer’s related brain changes in women with Parkinson’s

A team of neurologists and neuropathologists led by Dr Erika Driver Dunckley at the Mayo Clinic and Dr Thomas Beach at the Banner Sun Health Research Institute in Arizona has uncovered a striking biological difference in how the brains of men and women age with Parkinson's. Published in the 2026 issue of the Journal of Parkinson's Disease, their investigation revealed that women living with Parkinson's who also experience dementia are more than twice as likely as men to have a heavy build up of Alzheimer's related amyloid plaques in their brains. For a long time, medical textbooks treated neurological conditions as if they lived in entirely separate compartments. Parkinson's was strictly about movement and a protein called alpha synuclein, which clumps together to form Lewy bodies. Alzheimer's was all about memory and two different proteins, known as amyloid plaques and tau tangles. In reality, the human brain rarely reads the textbook. When researchers examine brain tissue after death, they frequently find what they call mixed pathology, meaning the physical hallmarks of both conditions are sharing the same space. In fact, more than half of the people who develop dementia alongside Parkinson's show significant physical signs of Alzheimer's in their brain tissue. What remained a mystery until now was whether biological sex influences this overlap. We already know that Parkinson's is diagnosed more frequently in men, whereas Alzheimer's is more common in women. To find out what happens when the two conditions intersect, the research team turned to the Arizona Study of Aging and Neurodegenerative Disorders and its Brain and Body Donation Program. They analysed the medical histories and donated brain tissue of 230 people who had lived with Parkinson's, comprising 156 men and 74 women. Throughout their lives, these volunteers had completed annual movement and memory assessments with specialist doctors, creating a detailed picture of how their symptoms evolved over an average of 14 to 15 years before they passed away in their early eighties. On the surface, the men and women looked remarkably similar during their clinic visits. They started noticing their first symptoms at roughly the same age, progressed through the physical stages of the condition at the same pace, and lived with it for the same number of years. There were a few familiar differences in their day to day experiences. Men were much more likely to act out their dreams during REM sleep and had higher histories of sleep apnoea, smoking, and alcohol use. Women retained a slightly better sense of smell and scored noticeably higher on verbal learning and word memory tests. Yet when it came to overall memory and thinking scores, or the percentage of people eventually diagnosed with dementia or mild cognitive impairment, there was no statistical gap between the sexes. The surprise was waiting under the microscope. When the neuropathologists examined the donated brain tissue, they found that the women carried a much heavier load of beta amyloid plaques than the men. Nearly 57 per cent of the women had a high concentration of these plaques across the outer layers of their brains, compared to just under 40 per cent of the men. These plaques had also spread deeper into specific movement and coordination centres of the women's brains, including the striatum, the substantia nigra, and the cerebellum. This difference held true even when the individuals had never received a formal diagnosis of Alzheimer's during their lifetime. Crucially, this biological divide depended heavily on the stage of cognitive decline. When the scientists looked solely at the 82 people in the study who had kept their sharp thinking or experienced only mild cognitive changes, the brains of men and women looked practically identical. The surge in amyloid plaques, alongside a higher density of Lewy bodies, appeared specifically in the 148 individuals who had developed Parkinson's dementia. In that group, more than 63 per cent of the women had a heavy plaque burden, compared to 44 per cent of the men. To make sure this wasn't just a coincidence caused by genetics or longevity, the statisticians accounted for the age at which each person died, the density of their Lewy bodies, and whether they carried the APOE e4 gene, which is a well known genetic risk factor for Alzheimer's. Even after stripping away those powerful influences, simply being female more than doubled the odds of accumulating high levels of amyloid plaques. Interestingly, the other culprit in Alzheimer's, the tau protein that forms twisted tangles inside brain cells, existed at the exact same levels in both men and women. This tells scientists that whatever is driving this difference in women is linked specifically to how the female brain processes or clears amyloid, rather than tau. That leaves a fascinating puzzle. If the women with dementia had so much more amyloid protein and a denser concentration of Lewy bodies in their brains, why weren't their memory and thinking test scores worse than the men's during life? The researchers point to two main explanations. First, in Alzheimer's research, tau tangles are often the strongest driver of severe memory loss, and since men and women had equal amounts of tau, their outward symptoms stayed on a par. Second, women may possess a form of biological cognitive resilience. Just as women tended to outperform men on verbal learning tests in the clinic, their brains might be better at compensating and working around the physical clutter of amyloid plaques for a longer time before outward symptoms show. Understanding what happens beneath the surface is much more than an academic exercise. As Dr Driver Dunckley pointed out following the study's release, medications designed to clear amyloid plaques from the brain are already approved and in use for certain people diagnosed with Alzheimer's. Knowing that women experiencing cognitive changes in Parkinson's are far more likely to harbour this exact same amyloid build up opens the door to investigating whether existing anti amyloid treatments could one day be repurposed to protect their thinking and memory. It is a compelling reminder that men and women do not always travel the exact same biological path with Parkinson's, and future clinical trials and treatments will need to tailor their approach accordingly.