A Secret to Early Brain Disease Detection

Earlier this year, Parkinson’s disease (PD) research entered a new era when the Michael J. Fox Foundation announced a momentous scientific breakthrough—the discovery of a biomarker for PD. It meant that, for the first time ever, we can now pinpoint the earliest known signs of the disease in Parkinson’s patients.

Reliable identification is essential for the treatment of brain disorders such as Parkinson’s, Huntington’s, ALS, and others, especially in those who are unaware that they are at risk. An unique scratch-and-sniff test can assist.

The “alpha-synuclein seeding amplification assay” (SAA), a much-needed new approach, may identify the misfolded alpha-synuclein in spinal fluid, the erroneous protein that is unmistakably connected to Parkinson’s disease. It distinguishes between those who have PD disease in their cells and those who do not, with an astounding 90% specificity. Similar to how elevated blood pressure or cholesterol levels are used to identify cardiovascular risk long before a heart attack sends a person to the emergency room, it does so even before symptoms appear.

This article originally appeared in our yearly trends bulletin, WIRED World in 2024. You can download a copy of the magazine or read other tales from the series here.

This article originally appeared in our yearly trends bulletin, WIRED World in 2024. You can download a copy of the magazine or read other tales from the series here.

As the first metric that can objectively identify individuals with the biology we’re targeting, the new SAA test is already being included into drug trials. This gives drugmakers greater confidence that they are evaluating experimental treatments in the appropriate populations. This fundamentally alters the investment’s value proposition for biopharma companies considering whether to join or remain in the high-risk neurological disease market. There will be a significant increase in the number of novel pharmaceuticals that are developed and make their way into pharmacy shelves in 2024.

As it turns out, your sense of smell is a surprisingly good predictor of brain disease. (We’re talking here not about the short-term smell loss associated with Covid-19, but significant and enduring smell loss that persists over years.) For a while now, researchers have known about the link between smell loss and neurodegeneration, especially in the presence of certain other risk factors, such as a diagnosis with REM behavior disorder (RBD), a sleep disorder. Research shows that half of those over age 60 are living with some degree of smell loss, yet the majority don’t realize it until they’re tested. If you couple this with the fact that all major brain diseases—Alzheimer’s, Parkinson’s, ALS, Huntington’s—are associated with some amount of smell loss, this is astounding.

The Michael J. Fox Foundation’s large-scale observational study of Parkinson’s set out to use poor smell as one of its criteria for finding and enrolling at-risk individuals. (We should note that, for this risk group, it’s still unclear if or when the disease may eventually show up.) The highly sophisticated screening device used? A humble scratch-and-sniff test, albeit the scientifically validated variety.

Until the SAA biomarker was validated, a reduced sense of smell couldn’t be objectively linked to the presence of underlying Parkinson’s disease biology. But now we can report that the test accurately diagnosed disease in 99 percent of people with poor smell and so-called sporadic Parkinson’s (in other words, those with no genetic mutation).

The process by which the SAA breakthrough was discovered is equally amazing. The “needles in a haystack” of people who unknowingly carry a higher chance of developing Parkinson’s disease but do not exhibit any traditional symptoms of the condition had to be located and studied in order to identify the biomarker. Determining the biology that distinguishes them from non-Powellian individuals was crucial. However, how can you locate someone who is unaware that they are being sought after?