Every tyre sheds. As a car drives, friction wears microscopic rubber off onto the road, and an additive meant to keep the tyre from cracking goes with it. That additive is called 6PPD. Once it meets ozone in the air it turns into 6PPD-quinone, and a new study says that second chemical may be bad news for the brain.
The trend underneath is a worry that has been building for years. 6PPD-quinone ends up in rivers and in road dust, and has repeatedly been found in human urine and blood. It is highly toxic to some aquatic animals such as salmon. In mice it has been shown to cross the blood-brain barrier, the filter that normally protects the brain from whatever is in the bloodstream.
What the researchers did
Chun Zhang, at Chongqing Three Gorges Medical College, and Jingqi Zhang, at Chengdu University of Traditional Chinese Medicine, set out to trace how the chemical might connect with Alzheimer’s at the molecular level. Their paper, “6PPD-Quinone Exposure and Alzheimer’s Disease: Insights from Integrative Network Pharmacology, Transcriptomics, Machine Learning, and Molecular Docking,” appeared in the journal Open Medicine. Neuroscience News described it as the first to look at this link systematically with data-driven computational methods.
They worked entirely on computers. First they used three pharmacological databases to guess which human proteins 6PPD-quinone could touch, and found more than a hundred. Then they pulled genes tied to Alzheimer’s from clinical and genetic databases. The two lists overlapped at 92 targets. A protein-protein network narrowed that to 23 core genes acting as communication hubs, busiest in the cerebral cortex and basal ganglia, regions involved in memory and movement that Alzheimer’s is known to hit.
Two datasets of post-mortem brain tissue let them check how those genes behave in real patients. One had 12 patients with the disease, 10 healthy older controls and 8 healthy young ones. The other had 44 patients and 46 healthy controls. The core genes showed significantly altered expression in the diseased brains, including genes that manage inflammation and cell damage.
Machine learning then picked out five genes that predict Alzheimer’s, and molecular docking simulations showed 6PPD-quinone binding strongly to three of them. The researchers say that could lead to oxidative stress, inflammation and breakdowns in communication between brain cells, setting the stage for the disease.
What it does not show
The caveats are large. The work is mostly computational and rests on gene datasets and a small number of brain samples. It does not prove the chemical damages human brain tissue, still less that it causes Alzheimer’s. Larger laboratory studies on cells, human tissue and animals are needed, the summary says, and so are epidemiological studies to find out how much everyday exposure actually raises risk.
The authors still call their work “the first systematic characterization of the molecular mechanisms by which 6PPD-Q may contribute to Alzheimer’s disease pathogenesis.”
Sources
- A common chemical from car tires might disrupt human brain cells (PsyPost)
- Invisible Tire Dust Hijacks Alzheimer's Predictor Genes (Neuroscience News)
