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Women who see themselves as having lower social status are more likely than other people to show early signs of heart stress linked to future disease risk, according to a new study led by researchers at McGill and Concordia universities.

One in three women in North America die from heart disease. Yet, women are less likely to receive important cardiac interventions or therapies than men. This highlights the need to rethink how we assess cardiovascular risk in women.”

Dr. Judy Luu, Co-Lead Author, Assistant Professor in McGill’s Department of Medicine and a clinician-scientist at the Research Institute of the McGill University Health Centre

Subjective social status – how people feel they rank compared to others in terms of their social standing – has previously been linked to physical and mental health, with lower social status associated with poorer health. The findings of this study are among the first to show measurable, sex-specific effects in the heart.

More than 400 adults between the ages of 35 and 83, all without diagnosed heart disease, took part in the study. Each completed a questionnaire ranking their social standing on a 10-rung ladder. Cardiac MRI scans then measured early signs of stress in the heart’s tissue.

Women who ranked their social status lower showed more signs of potential inflammation and early scarring in the heart, even when their income and education matched those who ranked their status higher. Men who ranked their social status lower than others with the same income and education did not show these warning signs.

Why might women be more affected?

There are two theories that may explain the findings, said co-lead author Jean-Philippe Gouin, Full Professor of Psychology at Concordia.

“First, subjective social status may better reflect women’s real-life experiences than objective data on their socioeconomic status,” he said. “For example, even with the same education as men, women often earn less or face additional social pressures. So, their self-perception may capture those realities more accurately.”

The second theory is about psychological impact, he said. Women may feel fewer opportunities for upward mobility, which can lead to more stress.

The researchers note that stress is one of the top five risk factors for heart disease in women under 65. Experiences such as trauma, discrimination, and caregiving demands may contribute to the subtle changes in heart tissue observed in this study – suggesting early signs of inflammation, even before disease is diagnosed.

The researchers plan to follow a larger group of participants over time to see whether these early markers predict heart disease.

“We hope our work helps shift the paradigm in cardiac care,” said Luu. “We want to make it normal to discuss mental wellness, social circumstances and stress in routine medical practice.”

A cancer immunotherapy drug that is already on pharmacy shelves is showing fresh potential in the fight against Parkinson’s disease.

In mouse experiments, nivolumab–relatlimab, a fixed‑dose antibody combination used for treating melanoma, blocked the cell‑to‑cell spread of toxic protein clumps that drive the disorder.

More than 8.5 million people worldwide are living with Parkinson’s disease. Current drugs ease symptoms but do little to halt the relentless loss of movement, speech, and independence.

Xiaobo Mao of Johns Hopkins University led an international team that traced the blockade to a newly revealed partnership between two brain proteins, Aplp1 and LAG‑3. Their study offers a practical target for slowing disease progression.

How cancer drug blocks Parkinson’s

Alpha‑synuclein normally helps nerve cells chat across synapses, yet when it misfolds it becomes sticky and forms Lewy bodies.

The group discovered that Aplp1 and LAG‑3 act like twin door handles, swinging the misfolded cargo into neurons together.

“Now that we know how Aplp1 and LAG-3 interact, we have a new way of understanding how alpha‑synuclein contributes to the disease progression of Parkinson’s disease,” confirmed Mao.

Deleting either handle in genetically engineered mice cut protein uptake, but deleting both slashed it by 90 percent.

Using cultured neurons, the team showed that antibodies against LAG‑3 disrupted the partnership and kept most toxic fibrils outside. That hint of druggability set the stage for tests with the approved melanoma therapy.

Repurposing a cancer drug for Parkinson’s

Nivolumab–relatlimab, marketed as Opdualag^TM, won FDA clearance in 2022 as the first combination to target PD‑1 and LAG‑3 checkpoints in tumors.

Because relatlimab binds LAG‑3, the Parkinson’s team wondered whether it could also short‑circuit the neural handshake.

They injected the antibody mix into mice previously dosed with pathogenic fibrils. Treated animals accumulated far fewer Lewy‑like inclusions, keeping the midbrain’s dopamine supply and motor skills intact.

“The anti‑LAG-3 antibody was successful in preventing further spread of alpha‑synuclein seeds in the mouse models,” said Ted Dawson, also from Johns Hopkins.

The effect outperformed complete genetic knockout of LAG‑3 because the drug simultaneously disrupted its partner, Aplp1.

A protein traffic jam in the brain

The brain’s substantia nigra houses dopamine‑producing neurons that fine‑tune movement. When alpha‑synuclein fibrils march from cell to cell, these neurons choke and die, triggering tremor and rigidity.

LAG-3 had been flagged as a fibril receptor before, yet blocking it alone left plenty of pathology. The new work clarifies that Aplp1 forms a complex with LAG-3, which creates a high‑affinity docking site for toxic cargo.

By filming neurons with pH‑sensitive dye, researchers watched fibrils enter healthy cells in minutes. Removal of either handle delayed entry, while removal of both stopped it almost completely.

The discovery may explain why single‑target strategies have struggled to translate. Therapies that ignore Aplp1 risk leaving a back‑door route open for disease spread.

Why Parkinson’s is so difficult

Parkinson’s is diagnosed only after motor symptoms emerge, by which time over half of nigral dopamine neurons have perished. Lewy bodies start forming decades earlier and appear to propagate along neural highways.

Scientists debate whether the fibrils cause disease or merely mark dying cells, yet the correlation is strong enough that reducing their spread remains a key goal.

Animal studies that limit fibril movement often preserve motor behavior and cortical thinking.

The Aplp1–Lag3 duo offers a concise molecular explanation for long‑range propagation. It also supplies a measurable biomarker, their physical interaction, that drug developers can monitor.

Antibodies in action

Preclinical success seldom guarantees human benefit, yet repurposing an approved therapy skips many safety hurdles.

Opdualag’s^TM pharmacokinetics, dosing, and adverse‑event profile are already mapped in thousands of cancer patients.

The antibody crosses the mouse blood–brain barrier at roughly 0.5 percent of plasma levels, similar to other IgG medicines. That level sufficed to curb fibril uptake and protect motor performance in pole and cylinder tests.

If forthcoming primate and human studies confirm brain penetration, clinicians could move swiftly into small Parkinson’s trials using this cancer treatment drug. Outcome measures might track motor scores, cerebrospinal fibril counts, and imaging of nigral dopamine.

Parkinson’s gets help from cancer drug

Cancer checkpoint drugs can unleash immune‑related side effects, including rash, thyroid imbalance, and fatigue. Whether similar events would occur at lower neurological doses remains unknown.

Another question is timing. Most cancer antibodies are delivered in pulses, whereas chronic neuroprotection for Parkinson’s patients might require years of therapy.

Finally, fibril spread is only one facet of Parkinson’s biology. Mitochondrial stress, environmental toxins, and genetics also contribute, so a combination of treatments will likely be needed.

Even so, the ease of testing an off‑the‑shelf cancer medicine for Parkinson’s patients makes this avenue irresistible. As Dawson observed, stopping spread “could significantly slow the progression of Parkinson’s disease.”

The study is published in Nature Communications.

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