A molecule in urine reveals how Parkinson’s breaks the brain’s waste disposal system
Two of the most well-known genetic risk factors for Parkinson’s disease both disrupt the same cellular process: waste disposal.
Researchers publishing in eLife investigated BMP — bis(monoacylglycerol)phosphate — a lipid molecule normally found inside lysosomes, the cellular structures that break down and recycle damaged proteins and other waste. BMP plays a role in forming small membrane vesicles inside lysosomes, which can be expelled from the cell as extracellular vesicles (EVs) and eventually reach the urine.
In Parkinson’s patients carrying mutations in LRRK2 or GCase — two genes linked to elevated Parkinson’s risk — urinary BMP levels are significantly elevated. The researchers wanted to understand why. Their conclusion: when LRRK2 or GCase (glucocerebrosidase, an enzyme that breaks down fats in lysosomes) malfunction, BMP accumulates inside lysosomes, and more BMP-enriched vesicles are expelled from cells. Those vesicles ultimately appear in urine at abnormally high concentrations.
A lysosomal problem at the heart of Parkinson’s
This matters because lysosomal dysfunction is one of the earliest and most consistent features of Parkinson’s — observable not just in brain cells, but throughout the body. Both LRRK2 and GCase are involved in maintaining lysosomal function. Mutations in either gene disrupt that maintenance, leading to the accumulation of cellular waste including alpha-synuclein, the protein that forms the toxic clumps characteristic of Parkinson’s disease.
The new finding — that disrupted lysosomal function translates into increased BMP secretion via extracellular vesicles — offers something tangible: a measurable signal in a body fluid that is easy to collect. That is valuable for diagnosis, but potentially also for tracking treatment response. If a therapy restores lysosomal function, urinary BMP should, in theory, decrease.
Not yet a clinical test
The study establishes that elevated urinary BMP correlates with LRRK2- and GCase-associated Parkinson’s, but it is not yet a validated biomarker ready for clinical use. Questions remain about specificity — does BMP also rise in other lysosomal storage disorders? — and about how early in the disease course the signal becomes detectable. Parkinson’s is characterized by a long presymptomatic phase, and early biomarkers are scarce. If urinary BMP turns out to be among the first measurable signals, it could enable earlier diagnosis and earlier intervention — at a stage when the brain has lost far fewer cells.