Mayo Autopsy Study: Women With Parkinson's Had Twice the Odds of Heavy Alzheimer's Plaque Burden

Women with Parkinson's disease had significantly more Alzheimer's-type amyloid plaque in their brains at death than men with the disease, according to a Mayo Clinic study published in the Journal of Parkinson's Disease this month. Mayo announced the work on Nov. 6.

The team examined 230 autopsy-confirmed Parkinson's cases drawn from the Arizona Study of Aging and Neurodegenerative Disorders and its Brain and Body Donation Program, run out of Banner Sun Health Research Institute in the Phoenix area.

The numbers

Female Parkinson's patients had a mean cortical total plaque score of 6.5 out of 15. Males averaged 4.9 out of 15 (p = 0.045).

Mean CERAD neuritic plaque density was 1.7 out of 3 in women and 1.3 out of 3 in men (p = 0.035).

A cortical plaque total of 5 or more turned up in 56.8% of women and 39.7% of men (p = 0.015).

The authors then ran a multivariable logistic regression controlling for ApoE ε4 status, Lewy body density score and age at death. Female sex was still associated with more than twice the odds of a plaque total of 5 or more (odds ratio 2.18; 95% confidence interval 1.17 to 4.06; p = 0.014). The authors conclude the association is independent of ApoE ε4, the gene variant most strongly tied to Alzheimer's risk.

What did not differ

The researchers found no difference between women and men in tau pathology, the other hallmark Alzheimer's protein. They also found no difference in levels of cognitive impairment.

That means more amyloid in women did not translate into measurably worse cognition in this group. The study does not explain why the plaque gap exists.

Mixed brains are common

Finding more than one neurodegenerative disease in a single brain is routine for brain banks. "A lot of patients have mixed pathologies, which means they may have been brought into the brain bank with one diagnosis, but then after we do autopsy studies, we actually identify they have multiple neurodegenerative diseases," said Dr. Erika Driver-Dunckley, a Mayo movement disorder neurologist and one of the lead researchers.

"It's not unusual for us to find mixed pathologies. The sex difference is what was interesting to us."

The authors note that earlier data from the same brain bank showed significant Alzheimer's co-pathology, amyloid and tau, in over half of Parkinson's disease dementia cases. They also point out that men are more often affected by Parkinson's, while women are more likely to develop Alzheimer's. Few studies had looked at sex differences in Alzheimer's pathology inside Parkinson's disease.

"What we found was, in women, particularly those with Parkinson's disease dementia, they had higher rates of Alzheimer's amyloid pathology," Driver-Dunckley said. The published paper is titled "Greater burden of Alzheimer's Co-pathology in women with Parkinson's disease dementia." The sex difference in plaque burden was present regardless of whether a co-occurring Alzheimer's diagnosis had been made.

Limits of the cohort

All participants were enrolled at Banner Sun Health Research Institute. Recruitment mainly targeted independently living retirees in Maricopa County, Arizona, so the group is predominantly Caucasian and of middle to high income. Participants got annual standardized assessments from neuropsychologists and movement disorders neurologists, then a comprehensive neuropathological exam after death.

It is an autopsy study. It describes brains after death and cannot show what causes the difference or how it plays out in living patients. Findings from a single, fairly homogeneous Arizona cohort have not been tested in broader populations.

The treatment question

The practical interest is drugs. Anti-amyloid medications are already approved for certain patients diagnosed with Alzheimer's disease. Parkinson's disease dementia, a severe late-stage condition, has no disease-modifying therapy.

Driver-Dunckley said the findings raise the possibility of studying whether those drugs could someday benefit certain patients with Parkinson's disease dementia who also have increased amyloid pathology. That is a research question. The study itself tested no treatment.

The researchers say the work could help scientists better understand how Parkinson's and Alzheimer's relate and point to new areas for treatment research. The next step is whether other brain banks, with more diverse donors, see the same female-skewed plaque burden, and whether anyone designs a trial around amyloid-positive Parkinson's dementia patients.

The paper appears in Journal of Parkinson's Disease, volume 16, issue 6, pages 1191 to 1200 (DOI: 10.1177/1877718X261470295).