Closing in on neurologic biomarker diagnosis

Aug 30 2012

By Eleanor McDermid, Senior medwireNews Reporter

A panel of five cerebrospinal fluid (CSF) biomarkers may help doctors to accurately diagnose patients with various forms of dementia and parkinsonian disorders, research published in the Archives of Neurology suggests.

In an editorial accompanying the study, Richard Perrin (Washington University School of Medicine, St Louis, Missouri, USA) notes that more work remains to be done, but says: "This study represents a significant step forward, demonstrating how a relatively modest panel of robust CSF protein biomarkers can categorize dementias and parkinsonian syndromes on the basis of pathology rather than clinical/behavioral changes."

The five biomarkers are α-synuclein, β-amyloid 1-42, total tau, phosphorylated tau, and neurofilament light chain.

Oskar Hansson (Skåne University Hospital, Malmo, Sweden) found that the first four of these biomarkers could distinguish 48 patients with Alzheimer's disease (AD) from 103 patients with other types of dementia (dementia with Lewy bodies or Parkinson's disease [PD] with dementia) with an accuracy of 90%.

The major contributors to this model were α-synuclein, total tau, and phosphorylated tau, which were all significantly increased in AD patients relative to those with other conditions and controls.

In all, the team assessed 453 CSF samples from patients with dementia or parkinsonian disorders and 107 from healthy volunteers.

The fifth biomarker - neurofilament light chain - distinguished 90 PD patients from 105 with atypical parkinsonism (progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy) with an accuracy of 93%. This was markedly increased in patients with atypical parkinsonism disorders. The other biomarkers did not add to the diagnostic accuracy of neurofilament light chain.

Perrin notes that the fact that the four AD biomarkers were " 'multiplexed' into a single high-throughput assay for this study makes this panel particularly appealing."

But he cautions: "It remains to be seen whether this panel might have utility to classify vascular dementia or the frontotemporal dementias, which were not included in this study; additional markers might be required for that purpose.

"It would also be worthwhile to know how this panel might perform in clinically ambiguous or seemingly straightforward cases that involve more than one proteinopathy."

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