A study led by the Mayo Clinic Arizona shows women with Parkinson’s disease have greater amyloid plaque burden than men with the condition, even after controlling for factors like carriage of the APOE4 Alzheimer’s disease susceptibility gene variant.
As reported at the European Academy of Neurology Congress in Geneva this week, 57% of women included in the study had a high amyloid plaque burden versus 40% of the men.
Amyloid-beta is a protein fragment that normally gets cleared from the brain. In Alzheimer’s disease, it misfolds and aggregates into oligomers and plaques between neurons. This disrupts synaptic signaling, activates neuroinflammation, and promotes tau protein hyperphosphorylation into neurofibrillary tangles as the disease progresses.
In contrast, Parkinson’s disease is caused by the misfolding and clumping of a protein called alpha-synuclein into toxic deposits known as Lewy bodies, which build up in and destroy the neurons that produce dopamine in a brain region called the substantia nigra. While Parkinson’s is known for its characteristic motor symptoms, at least 25% also have dementia-like symptoms similar to those seen in Alzheimer’s disease. Amyloid beta plaques are thought to worsen Parkinson’s disease and increase the risk of dementia symptoms.
There are known differences in the prevalence and symptoms shown by men and women with Parkinson’s disease. To investigate this further, 230 people enrolled in the Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program were included in this study after death. Amyloid burden in the brain was assessed during autopsy. Other clinical factors such as cognition and symptoms were recorded prior to death.
The study found that amyloid plaque burden in women was higher than in men with Alzheimer’s. For example, mean cortical total plaque score in women was 6.5/15 vs 4.9/15 in men. Neuritic plaque density was also higher in women at 1.7/3 compared with 1.3/3 in men.
After correcting for age at death and APOE4 status, women in the study were more than twice as likely to have a high plaque burden than men.
This did not seem to translate to cognitive differences between men and women in the study though. “Men and women with Parkinson’s disease had similar rates of Alzheimer’s dementia and similar results on cognitive testing. However, women showed a higher amyloid plaque burden compared with men,” explained presenting author Erika Driver-Dunckley, MD, Mayo Clinic Arizona, in a press statement.
Notably, in standard Parkinson’s disease, men are at higher risk of developing dementia than women, so it is possible women have some protection from alpha-synuclein-driven decline but not from damage linked to amyloid accumulation. Women with Parkinson’s also live longer than men with the condition, as well as being more prone to amyloid buildup and Alzheimer’s disease, which complicates understanding the meaning of these results.
“Our findings highlight the need for further research into sex differences in Parkinson’s disease and Alzheimer’s-related pathology,” concluded Driver-Dunckley. “An important next step will be to confirm these findings in additional large clinicopathological studies and better understand the biological mechanisms that may underlie these differences.
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