A form of Parkinson’s disease caused by mutations in a gene known as PINK1 has long been labelled rare. But our research shows it’s anything but – at least for some populations.

Our meta-analysis revealed that people in specific Polynesian communities have a much higher rate of PINK1-linked Parkinson’s than expected. This finding reshapes not only our understanding of who is most at risk, but also how soon symptoms may appear and what that might mean for treatment and testing.

Parkinson’s disease is often thought of as a single condition. In reality, it is better understood as a group of syndromes caused by different factors – genetic, environmental or a combination of both.

These varying causes lead to differences in disease patterns, progression and subsequent diagnosis. Recognising this distinction is crucial as it paves the way for targeted interventions and may even help prevent the disease altogether.

Why we focus on PINK1-linked Parkinson’s

We became interested in this gene after a 2021 study highlighted five people of Samoan and Tongan descent living in New Zealand who shared the same PINK1 mutation.

Previously, this mutation had been spotted only in a few more distant places –Malaysia, Guam and the Philippines. The fact it appeared in people from Samoan and Tongan backgrounds suggested a historical connection dating back to early Polynesian migrations.

One person in 1,300 West Polynesians carries this mutation. This is a frequency well above what scientists usually classify as rare (below one in 2,200). This discovery means we may be overlooking entire communities in Parkinson’s research if we continue to assume PINK1-linked cases are uncommon.

Traditional understanding says PINK1-linked Parkinson’s is both rare and typically strikes younger people, mostly in their 30s or 40s, if they inherit two faulty copies of the gene. In other words, it’s considered a recessive condition, needing two matching puzzle pieces before the disease can unfold.

Our work challenges this view. We show that even one defective PINK1 gene can cause Parkinson’s at an average age of 43, much earlier than the typical onset after 65. That’s a significant departure from the standard belief that only people with two defective gene copies are at risk.

Why this matters for people with the disease

It’s not just genetics that challenge long-held views. Historically, PINK1-linked Parkinson’s was thought to lack some of the classic features of the disease, such as toxic clumps of alpha-synuclein protein.

In typical Parkinson’s, alpha-synuclein builds up in the brain, forming sticky clumps known as Lewy bodies. Our results, contrary to prior beliefs, show that alpha-synuclein pathology is present in 87.5% of PINK1 cases. This finding opens up a promising new avenue for future treatment development.

The biggest concern is early onset. PINK1-linked Parkinson’s can begin as early as 11 years old, although a more common starting point is around the mid-30s. This early onset means living longer with the disease, which can profoundly affect education, work opportunities and family life.

Current treatments (such as levodopa, a precursor of dopamine) help manage symptoms, but they’re not designed to address the root cause. If we know someone has a PINK1 mutation, scientists and clinicians can explore therapies for specific genetic pathways, potentially delivering relief beyond symptom management.

Sex differences add a layer of complexity

In Parkinson’s, generally, men are at higher risk and tend to develop symptoms earlier. However, our findings suggest the opposite pattern for PINK1-linked cases. Particularly, women with two defective copies of the gene experience onset earlier than men.

This highlights the need to consider sex-related factors in Parkinson’s research. Overlooking them risks missing key elements of the disease.

Genetic testing could be a game-changer for PINK1-linked Parkinson’s. Because it often appears earlier, doctors may not recognise it immediately, especially if they are more familiar with the common, later-onset form of Parkinson’s.

Early genetic testing could lead to a faster, more accurate diagnosis, allowing treatment to begin when interventions are most effective. It would help families understand how the disease is inherited, enabling relatives to get tested.

In some cases, where appropriate and culturally acceptable, embryo screening may be considered to prevent the passing of the faulty gene.

Knowing you have a PINK1 mutation could also make finding the right treatment more efficient. Instead of a lengthy trial-and-error process with different medications, doctors could use emerging therapies designed to target the underlying PINK1 mutation rather than relying on general Parkinson’s treatments meant for the broader population.

Addressing research gaps

These findings underscore how crucial it is to include diverse populations in health research.

Many communities, such as those in Samoa, Tonga and other Pacific nations, have had little to no involvement in global Parkinson’s genetics studies. This has created gaps in knowledge and real-world consequences for people who may not receive timely or accurate diagnoses.

Researchers, funding bodies and policymakers must prioritise projects beyond the usual focus on European or industrialised countries to ensure research findings and treatments are relevant to all affected populations.

To better diagnose and treat Parkinson’s, we need a more inclusive approach. Recognising that PINK1-linked Parkinson’s is not as rare as previously thought – and that genetics, sex differences and cultural factors all play a role – allows us to improve care for everyone.

By expanding genetic testing, refining treatments and ensuring research reflects the full spectrum of Parkinson’s, we can move closer to more precise diagnoses, targeted therapies and better support systems for all.

Victor Dieriks, Research Fellow in Health Sciences, University of Auckland, Waipapa Taumata Rau and Eden Paige Yin, PhD candidate in Health Sciences, University of Auckland, Waipapa Taumata Rau

This article is republished from The Conversation under a Creative Commons license. Read the original article.