A urine marker points to disrupted waste management in brain cells in Parkinson's disease
Two of the best-known genetic risk factors for Parkinson's disease both appear to disrupt the same molecular link: the cell's waste-disposal system. And that disruption shows up in urine, opening the door to a test for brain damage that you would otherwise never be able to see from the outside.
Researchers have published a study in eLife on BMP, or bis(monoacylglycerol)phosphate, a lipid molecule that normally resides inside cellular lysosomes. Lysosomes are the cell's waste-processing factories: they break down damaged proteins and other debris. BMP plays a role in forming small vesicles within lysosomes, which can then be expelled from the cell as what are known as extracellular vesicles.
In Parkinson's patients carrying mutations in LRRK2 or GCase, two genes linked to an increased risk of Parkinson's disease, urinary BMP levels are significantly elevated. The researchers wanted to understand why. Their conclusion: when LRRK2 or GCase (glucocerebrosidase, an enzyme that breaks down fat inside lysosomes) stops working properly, BMP accumulates in the lysosomes, and more BMP-rich vesicles are pushed out of the cell. Those vesicles ultimately end up in the urine.
A window into the lysosomal system
This matters because lysosomal dysfunction is one of the earliest and most consistent features of Parkinson's disease, even outside the brain. Both LRRK2 and GCase are involved in maintaining the lysosomal system. Mutations in these genes disrupt that maintenance, leading to a build-up of waste products inside cells, including alpha-synuclein, the protein that forms the characteristic clumps seen in Parkinson's disease.
The new finding, that impaired lysosomal function translates into increased BMP secretion via extracellular vesicles, offers something tangible: a measurable readout in a body fluid that is easy to obtain. That is valuable for diagnostics, but potentially also for tracking treatment effects. If a therapy restores lysosomal function, BMP levels in urine should fall.
Not a diagnostic test yet
The study makes clear that elevated urinary BMP correlates with LRRK2- and GCase-mediated Parkinson's disease, but it is not yet a validated biomarker. Questions remain about specificity, does BMP also rise in other lysosomal disorders?, and about how early in the disease the signal becomes detectable. Parkinson's disease is characterised by a long pre-symptomatic phase, and early biomarkers are scarce. If BMP turns out to be one of the first measurable signals, that could make earlier diagnosis and intervention possible.