A blood test for Parkinson’s disease?
Volume 12, Issue 2 | June 12, 2025
ALSO IN THIS ISSUE
Is loss of Y chromosome coming to Dx panels?
Measles and COVID updates
Looking for the Goldilocks level of breast-cancer screening
When genomic screening yields actionable results, most patients aren’t aware
Loss of Y chromosome – coming to a Dx panel near you?
The Y chromosome has long been almost ignored. Having lost 97% of its original genes, it is now the smallest of the 22 chromosomes, and it was fully sequenced only recently. It’s responsible only for sperm production and for determining birth sex in the fetus - or so we thought.
Recent work published in Nature (open access) and summarized in the New Scientist (paywall) suggests that little Y has more to do than we had realized. Among other things, it controls many immune responses. When Y is lost, tumors are more aggressive, and neurodegeneration and heart failure are more prevalent. Informed speculation suggests that its selective loss in older men may account for up to half of their lower life expectancy than women.
COMMENTARY: It used to be thought that loss of the Y chromosome (LOY) was just one more feature of the natural genomic instability that increases with age. But as research has advanced (especially in Dan Theodorescu’s lab, now at the University of Arizona), it has become increasingly clear that LOY doesn’t just correlate with diseases of aging - it can cause those diseases, as well.
We still don’t know exactly how Y loss leads to problems, though. It’s particularly important that we learn how LOY affects the immune system, because, as this research shows, it affects how well immunotherapy works as a cancer treatment. (When Y is lost, T-cells are less effective. That generally leads to higher mortality, but it makes immunotherapy like CAR-T and PDL1/PD1 checkpoint inhibition more effective.) Testing for LOY should rapidly become a standard part of men’s cancer diagnosis.
A simple blood test for Parkinson’s disease?
Two years ago, we reported on a Parkinson’s disease (PD) test that would dramatically improve early detection. Using cerebrospinal fluid (CSF) as a sample, which requires a spinal tap, it had impressive accuracy of 88% sensitivity and 96% specificity. A recent report in Nature Aging suggested that a simple PCR-based blood test for PD-specific transfer RNA (tRNA) fragments might be a useful first test before ordering the more invasive CSF diagnostic.
The clinical scoring system currently used to diagnose PD is called the Unified Parkinson’s Disease Rating Scale. It’s essentially 100% sensitive and specific once motor problems appear, but doesn’t do nearly as well with patients in earlier stages of the disease. This test detects tRNA fragments that are involved in the protein translation and energy-management deficiencies that begin in early PD. It has only moderate accuracy (78% sensitivity and 52% specificity), but is substantially better than UPDRS.
COMMENTARY: This is an intriguing approach that suggests novel disease biology, previously ignored possible biomarkers, and new avenues for treatment development, all in one complex paper (see attached methodology – Extended Data Fig. 1). The possibilities for improved definitive PD diagnosis are exciting on their own, if the work proves to withstand reproducibility. In addition, the paper stands as yet another example of how artificial intelligence applied to noninvasive samples is beginning to revolutionize diagnostics.
FDA’s Final Rule on LDTs is officially dead
When a judge vacated the FDA’s Final Rule on laboratory-developed tests (LDTs), the agency was given 60 days to challenge the decision. FDA didn’t take action. Since their time to do so has now run out, the ruling was not appealed and the rule will not go into effect.
Measles: First national wastewater monitoring system
Jump in new cases linked to travel and more outbreaks
Administration cuts leave global surveillance network with no funding
WastewaterSCAN has put together the first national wastewater monitoring system for measles. It has testing sites in 40 states and has detected the virus in California, Connecticut, and Maryland so far. According to the Pandemic Center at the Brown University School of Public Health, the presence of measles in wastewater indicates that the disease is being transmitted among people in the community. Measles hasn’t been reported in any of the three cities where WastewaterSCAN found it, which suggests that the virus is spreading undetected in those locations.
The CDC reported 80 new measles cases last week, the largest weekly number since April. “In a shift, most of the new cases appear to be linked to travel and an increasing number of outbreaks rather than the large outbreak centered in West Texas,” CIDRAP reported.
“The Trump administration’s gutting of global aid is threatening to collapse a critical network of laboratories responsible for measles and rubella surveillance around the world,” STAT News reported this week. The Global Measles and Rubella Laboratory Network (GMRLN) run by the WHO, was entirely funded by America’s CDC. The administration’s cuts have left it without any source of funding at all. The WHO Foundation is working to raise money from philanthropic donors to keep the network alive.
The current larger outbreaks are shown below. The cases in Texas, New Mexico, Kansas, and Oklahoma all came from the same source; those in Arkansas, Colorado, Montana, North Dakota and Ohio are unrelated. The outbreak in Michigan has ended.
COVID’s new strain
The WHO has put a new strain of the virus on its watch list: NB.1.8.1. It's more contagious than the most recent strains, but doesn't appear to cause more severe illness. (For those who want the stats: Your Local Epidemiologist reports that it has about a 65% growth advantage over the current strain. For comparison, the original Omicron had about a 500% growth advantage over the strain it replaced.)
COMMENTARY: Are we doing the right amount of breast-cancer screening?
Breast-cancer screening has been strikingly successful - it’s estimated to have reduced deaths from the disease by 20% over the past 20 years. But could we do better?
In August 2020, HHS’s Healthy People 2030 initiative aimed to get 80.3% of healthy 50- to 74-year-old women to receive a mammogram once every two years. We’ve gotten pretty close: A recent analysis of the 2019 US National Health Interview Survey reported that 77.2% had a mammogram in the prior two years.
What does this look like on the ground? Two-thirds of screening for all ages is carried out annually, and 60% of those over 74 continue to test at least every two years (with 2/3 screening every year). And while the overall percentage of people getting screened is below the Healthy People 2030 goal, it’s by far the highest coverage of any cancer-screening program. But is that goal what we should be aiming for?
It depends on who you ask. Healthy People 2030 goes by the recommendations from the US Preventive Services Task Force. The American Cancer Society, on the other hand, recommends the following:
Optional screening from ages 40 - 44
Annual screening from 45 - 54
Screening every one to two years for ages 55 and up
Bottom line: Until we have a study in hand that tells us which protocol leads to lower mortality, we won’t know which is the right one. Until then, each person and their health-care provider(s) will need to make individual decisions.
When genomic screening yields actionable results, most patients don’t hear about it
Genomic screening of more than 175K people found that about 6,000 of them had “medically actionable” results - results that indicated there was something they could do to improve their health or prevent disease. About 90% of those folks didn’t know they had genes that put them at risk of health problems.
The results, published this week in JAMA Network Open, come from a study done through a single health-care system’s biobank. The authors also noted that only 25% of similar biobanks notify their patients of potentially actionable results.
COMMENTARY: This seems like a great opportunity to improve health using samples and data that already exist. The concern, of course, is privacy and the ever-present specter of being refused insurance coverage due to pre-existing conditions. Until those issues are resolved, it’s hard to imagine that biobanks will routinely give their patients this information, no matter how helpful it might be.