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The hunt is on. (dowell/Getty Images)
Scientists in Barcelona, Spain, think they have identified a possible biomarker that can predict the onset of a disorder that gives rise to diseases like Parkinson's long before symptoms of cognitive and physical decline appear.
These specific indicators swimming in the blood and cerebrospinal fluid (CSF) precede most physical and cognitive symptoms of Parkinson's and dementia, potentially giving individuals more time to prepare for, or one day even prevent, the conditions.
Unfortunately, most external symptoms of Parkinson's don't manifest until the vast majority of dopamine neurons have already been damaged, and telltale protein clumps called Lewy bodies are no help for living patients as they can only be verified upon autopsy.
An early form of diagnosis is desperately needed to halt or slow down the disease before it worsens. Now, researchers think they have found an early biomarker in the blood that is tied to the way cells release energy.
In human cells, including neurons, not all DNA is cooped up within the nucleus. The part of a cell that generates energy, the mitochondria, has its own genetic material, called mitochondrial DNA (mtDNA), which comes only from your mother.
However, mitochondria are busy little power factories that also produce waste products in the form of reactive oxygen species, or free radicals, which can be toxic if they aren't cleared out and recycled properly.
This positioning of mtDNA so close to where free radicals are readily produced is thought to be one reason why mtDNA is relatively vulnerable to dysfunction over time, compared to DNA tucked safely away in the envelope of the nucleus.
As such, mtDNA can accumulate mutations easily, leading to mitochondrial inefficiencies. Compared to other cells of the body, neurons have high energy demands, which means if their mitochondria aren't working at full capacity, neither are they.
Emerging evidence suggests that mitochondrial dysfunction is closely associated with the onset of Parkinson's and a form of dementia associated with Lewy bodies. But it's remained unclear if damaged mtDNA molecules are predictive of the disease, showing up in the earliest days, or if they are a byproduct of the disease, showing up later.
The new findings from Spain add weight to the former case.
The study focused on 17 patients with idiopathic rapid eye movement sleep behavior disorder (IRBD), which causes unpleasant dreams and vigorous physical behaviors during REM sleep. This disorder is commonly experienced by those who later get diagnosed with Parkinson's disease or dementia with Lewy bodies. In fact, it's one of the earliest signs of Parkinson's, which takes a notoriously long time to manifest externally.
The team compared the bloodwork and CSF of IRBD patients with 34 other patients, who also had IRBD but who later developed Parkinson's or Lewy body dementia as well. The control group consisted of 20 age-matched adults without IRBD, Lewy body dementia, or Parkinson's.
Ultimately, the team of researchers, led by Margalida Puigròs at the Institute of Biomedical Research of Barcelona, found significantly more damaged mtDNA molecules in the CSF of patients with IRBD, and those who later also received a diagnosis for Parkinson's disease or Lewy body dementia, compared to unaffected controls.
People with IRBD who went on to develop a Lewy body disorder also had more copies of damaged and intact mtDNA in their blood serum, compared to those who didn't develop either PD or Lewy body dementia, or never had IRBD.
In a second subgroup analysis, 11 patients with IRBD who had not yet been diagnosed with Parkinson's were tracked over time. Those who later developed Parkinson's or Lewy body dementia showed similar numbers of damaged mtDNA molecules compared to those who did not develop a Lewy body disorder.
This suggests high levels of damaged mtDNA are "already present in IRBD and long before converting to a Lewy body disorder," the researchers write in their paper.
Meanwhile, people who had higher numbers of damaged mtDNA molecules in their CSF samples usually received a diagnosis of Parkinson's or Lewy body dementia earlier.
"We have observed that the amount of [mt]DNA with deletions is related to the time it takes for patients with sleep behavior disorder to manifest clinical symptoms of Parkinson's disease," says Puigròs.
This correlation suggests that mtDNA dysfunction may be "a critical molecular mechanism in the early stages of neurodegeneration."
For years, scientists have worked to develop early tests based on bloods, skin swabs, and eye scans to diagnose Parkinson's before it causes motor and cognitive decline. And while no reliable screening test has made it to market quite yet, with every study, experts inch closer to that possibility.
The emerging link between the brain's energy metabolism and Parkinson's is providing some of the most promising leads yet.
The study was published in eBioMedicine.