Our understanding of Parkinson’s disease (PD) is evolving, and with it, so is our perception of PINK1-related Parkinson’s disease (PINK1-PD). Historically, PINK1-PD has been viewed as a rare genetic condition that does not involve the formation of toxic alpha-synuclein clumps. However, this oversimplified narrative has largely been shaped by a lack of extensive studies in diverse populations.

At the Faculty of Medical and Health Sciences, University of Auckland, our latest meta-analysis led by my talented PhD student, Eden Yin, and published in the Journal of Parkinson’s Disease, reveals a more nuanced and complex picture of PINK1-PD. Here’s what we found:
Key Findings
Regional Prevalence:
In some regions, up to 9% of early-onset Parkinson’s cases are linked to PINK1 variants.
One specific damaging variant, p.Leu347Pro, affects approximately 1 in 1300 West Polynesians, exceeding the threshold for what is considered a “rare” disease.
Earlier Disease Onset:
Individuals with two defective PINK1 genes typically develop Parkinson’s symptoms around age 35.
Those with one defective PINK1 gene show similar symptoms but at a later age, around 43 years old. Both of these are much earlier than the typical onset of Parkinson’s, which generally occurs after age 65.
Gender Differences:
Women with PINK1-PD tend to develop symptoms earlier than men, a significant finding since Parkinson’s typically manifests later in women compared to men. This gender disparity is particularly pronounced in individuals with two defective PINK1 genes.
Alpha-Synuclein Clumps:
Contrary to the belief that PINK1-PD is free of alpha-synuclein involvement, most PINK1-PD brains analyzed post-mortem show alpha-synuclein clumps, highlighting the role of this toxic protein in the disease.
Implications
These findings challenge the conventional characterization of PINK1-PD as a rare and straightforward genetic form of Parkinson’s disease. Instead, they reveal a condition shaped by:
Genetic factors, such as one or two defective PINK1 genes.
Sex differences, with unique implications for disease onset.
Protein involvement, particularly the formation of alpha-synuclein clumps.
Given the higher prevalence of PINK1 variants in certain populations, such as West Polynesians, it is clear that PINK1-PD is not as rare as previously thought. These insights underscore the urgent need for:
Increased research into PINK1-linked Parkinson’s disease, especially in New Zealand and the Pacific.
Greater recognition of its complexity and global prevalence.
Targeted interventions to address the unique challenges posed by this form of Parkinson’s.
Moving Forward
PINK1-PD represents a critical piece of the Parkinson’s puzzle. By understanding its unique genetic, gender, and protein-related characteristics, we can pave the way for earlier diagnoses, more tailored treatments, and improved outcomes for those affected by this under-recognized form of Parkinson’s disease. If you want to know more. You can find the full article here.
We invite you to join the conversation and help raise awareness of PINK1-PD. Together, we can push for the recognition and research this condition deserves.
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