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Two Studies Investigate Sex-Based Differences in Parkinson's and Alzheimer's Disease Pathology

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Biological Sex May Influence Protein Accumulation in Parkinson’s and Alzheimer’s Diseases

A series of findings presented at medical conferences and published in peer-reviewed journals examine how biological sex may influence the accumulation and interaction of proteins associated with Parkinson's disease and Alzheimer's disease.

Study 1: Amyloid Plaque Burden in Parkinson's Disease

Mayo Clinic Arizona | European Academy of Neurology Congress 2026

Data Source and Methods

Researchers from Mayo Clinic Arizona analyzed data from 230 autopsy-confirmed Parkinson's disease cases. The cases were drawn from the Arizona Study of Aging and Neurodegenerative Disorders and the Brain and Body Donation Program.

Key Findings on Amyloid Plaques

  • Women had a mean cortical total plaque score of 6.5 out of 15, compared to 4.9 out of 15 for men (p=0.045).
  • Women had a greater neuritic plaque density score: 1.7 out of 3 versus 1.3 out of 3 for men (p=0.035).
  • High plaque burden was observed in 56.8% of women, compared to 39.7% of men (p=0.015).

After adjusting for age at death and APOE ε4 status, women were more than twice as likely as men to have a high amyloid plaque burden (odds ratio 2.18; 95% confidence interval 1.17–4.06; p=0.014).

Cognitive Outcomes

No statistically significant differences were found between men and women in rates of Alzheimer's dementia diagnosis or cognitive test performance.

Researcher Statement

Lead author Dr. Erika Driver-Dunckley stated that the findings suggest women may be more susceptible to amyloid-driven pathology in Parkinson's disease. She noted that while the greater plaque burden did not correspond to cognitive differences in this study, a larger study might detect such differences.

Study 2: Interaction of Alpha-Synuclein and Tau Proteins

Mayo Clinic | Published in JAMA Network Open

Data Source and Methods

A separate study investigated whether coexisting abnormal protein buildups alter disease progression differently between sexes. Researchers analyzed data from 415 participants in the Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid tests were used to identify abnormal alpha-synuclein, a protein linked to Parkinson's disease, and repeated brain imaging was used to measure accumulation of tau protein, a marker of Alzheimer's disease.

Key Findings

  • Approximately 17% of participants showed abnormal alpha-synuclein.
  • Among participants with both Alzheimer's-related pathology and abnormal alpha-synuclein, women accumulated tau protein at a significantly faster rate than men with the same coexisting protein changes.

The study reported that Alzheimer's-related brain changes progressed up to 20 times faster in women who also exhibited abnormal alpha-synuclein, a pattern not observed in men.

Context from Researchers

Dr. Kejal Kantarci, a Mayo Clinic neuroradiologist and senior author, stated that recognizing these sex-specific differences could inform more targeted clinical trials and personalized treatment strategies.

Dr. Elijah Mak, first author of the study, noted that the finding opens new avenues for understanding the disproportionate burden of dementia in women and may reveal new therapeutic targets.

Limitations and Future Directions

The researchers stated that further study is required to determine if these sex-specific effects are also present in patients with dementia with Lewy bodies, where alpha-synuclein is the primary disease driver. This would help clarify whether the observed difference is specific to Alzheimer's disease or indicative of a broader sex-specific vulnerability across neurodegenerative conditions.