Fibronectin protein blood levels seen to predict a disability’s start
Lower levels tied with faster onset of a milestone like wheelchair reliance
Blood levels of the fibronectin protein could be used as a predictor of disability in people with Parkinson’s disease, according to a recent study.
Lower levels of the protein, referred to as plasma fibronectin (pFN), associated with a shorter time to reaching the start of a disability milestone like repeat falls or the need for a wheelchair, its researchers reported. Likewise, faster declines in pFN over time correlated with faster disease progression.
Biological changes known to associate with Parkinson’s, including alpha-synuclein levels and a disturbed blood-brain barrier, also linked with pFN levels.
“Taken together, these analyses suggest that pFN is a clinically useful prognostic biomarker that could potentially be used to predict disease prognosis, monitor disease progression, and reflect brain pathological changes,” the researchers, all with institutes in China, wrote.
Disability levels in Parkinson’s reflect disease progression
The study, “Plasma fibronectin is a prognostic biomarker of disability in Parkinson’s disease: a prospective, multicenter cohort study,” was published in npj Parkinson’s disease.
People with Parkinson’s accumulate disability due to progressively worsening disease motor and nonmotor symptoms.
Reaching certain disability levels — known as disability milestones, and referring to the start of wheelchair reliance or dementia affecting daily life — is associated with a poorer prognosis and shorter survival times for Parkinson’s patients, the researchers noted. Prognosis refers to a disease’s likely course or outcomes.
But progression in this neurodegenerative disease can be highly variable, making it difficult to predict if or when a given patient will reach a given disability level.
“Prognostic biomarkers for milestones in PD [Parkinson’s disease] are urgently needed, particularly ones that could also dynamically monitor PD progression,” the researchers wrote.
As inflammation is thought to play a key role in disease progression, biomarkers of such inflammation might be used to predict a person’s likely disability course.
The scientists opened a clinical study (ChiCTR2100045714) to identify which of 19 blood biomarkers of inflammation in patients, all recruited through hospitals in the South China Parkinson’s Disease Alliance, might best predict disability milestones.
Their analyses involved two patient groups: a discovery group (218 adults) to identify the best possible biomarkers, and a 84-patient validation group to verify initial findings.
Fibronectin helps cells adhere to each other, with a role in wound repair
They developed and used a prediction model to ascertain which of the 19 inflammatory biomarkers (ranging from cholesterol and uric acid levels to fibronectin protein levels), as well as certain clinical features (like disease duration, age, or sex) best predicted a patient’s milestone prognosis.
A poor prognosis was assigned to people who had reached any of six disability milestones: recurrent falls, wheelchair dependence, admission to a care home, severe hallucinations, dementia, or death.
Analyses found that pFN levels at an initial study visit (baseline level) were the best independent predictor of prognosis, with lower levels associated with a higher risk of reaching disability milestones.
Fibronectin is a protein involved in helping cells adhere to each other, important for processes like wound repair. Its levels are known to decrease during inflammation, although for reasons that are not fully understood.
People with higher pFN blood levels — at or above a cutoff of 197.6 mg/L — lived for a significantly longer time before reaching a first disability milestone after a disease diagnosis, than did those with levels below that cutoff, demonstrating “that pFN is a prognostic biomarker for predicting disability milestones in PD patients,” the researchers wrote.
Scientists then explored whether changes in pFN levels reflected the rate of disease progression among 96 patients (32% of the discovery group) with follow-up observational data reaching out a median of 5.5 years from baseline.
Patients were categorized as having mild disease progression if they reached a first milestone five or more years after disease onset, and aggressive progression if they reached it in less than five years.
Protein levels fell more quickly each year with aggressive Parkinson’s
Significantly faster annual declines in pFN levels within the first five years after onset were seen in people with aggressive disease, compared with those having mild disease.
The annual rate of change in pFN levels also significantly correlated with the annual change in Hoehn and Yahr stages — a standard clinical measure of Parkinson’s motor disability — in patients with mild or aggressive disease. This finding, the researchers wrote, suggested that “dynamic changes” in fibronectin could be a way of monitoring disease progression.
pFN levels also were found to correlate with biological changes known to associate with Parkinson’s. Specifically, lower pFN levels linked with higher blood levels of a toxic form of the alpha-synuclein protein known to accumulate in patients’ brains. In imaging scans of validation group patients, lower protein levels also associated with greater blood-brain barrier permeability.
A protective membrane working to prevent harmful substances circulating in the blood from reaching the brain, this barrier is known to become leakier, or more permeable, as Parkinson’s progresses.
“We selected 19 inflammatory markers that can be conveniently tested in clinical routine practice,” the researchers wrote. “Our study highlights a novel prognostic biomarker, that is, baseline plasma [fibronectin] as a best-performing biomarker for predicting the rate of onset of milestones in PD individuals.”
Study findings “have potential clinical relevance as the identified pFN biomarker can be used to predict clinical prognosis, and be used as an outcome measure for clinical trials aimed at delaying or preventing the onset of disability milestones in PD,” the team concluded.
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