News

Biomarkers May Aid Differential Diagnosis of Dementias, Parkinsonism

View on the News

How Robust in Early Disease?

"The strengths of this validation study are in its synthesis of these candidate markers into a broadly applicable working panel, and the size and quality of its CSF collection," wrote Dr. Richard J. Perrin.

However, these CSF samples were taken from "relatively ideal clinical examples," involving patients who were "symptomatic and presumably well into their course of pathology. It remains unclear whether the biomarker changes of the entire panel observed at these stages will also be detectable and diagnostic during the early symptomatic or presymptomatic stages," he noted.

Because the investigators did not include vascular dementia or the frontotemporal dementias, further studies will need to determine whether this panel also has utility for their diagnosis or if additional markers might be required for that purpose. Like most current studies, the study also has the weakness of lacking postmortem neuropathologic assessments, he wrote.

Dr. Perrin is in the department of pathology and immunology and at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, both at Washington University, St. Louis. He reported no financial conflicts of interest. These remarks were taken from his editorial comment accompanying Dr. Hall’s report (Arch. Neurol. 2012 Aug. 27 [doi:10.1001/archneurol.2012.2353]).


 

FROM ARCHIVES OF NEUROLOGY

Measurements of five protein biomarkers in the cerebrospinal fluid helped to differentiate Alzheimer’s disease from Parkinson’s disease with dementia and from dementia with Lewy bodies in a cross-sectional study of individuals at Swedish neurology and memory disorder clinics.

The diagnostic accuracy of this panel of tests in distinguishing Alzheimer’s disease from dementia with Lewy bodies "is at least in the same order of magnitude as that obtained with dopamine transporter imaging, and with a lower cost," Dr. Sara Hall of the department of clinical sciences, Lund (Sweden) University, Malmö, and her associates wrote in a study published Aug. 27 in Archives of Neurology.

In addition, one of the five biomarkers in this panel appears to differentiate Parkinson’s disease from atypical parkinsonism such as that seen in progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, the researchers noted.

Their results confirmed those of previous studies postulating that CSF total tau (T-tau) and phophorylated tau (P-tau) levels are higher in Alzheimer’s than in the other two dementias, whereas amyloid-beta (Abeta) 1-42 levels are lower in Alzheimer’s than in the other two dementias.

Levels of alpha-synuclein reflect Lewy body pathology, which is typically absent in Alzheimer’s but present in the other two dementias. This study verified that there is a clear difference in these levels between patients who have Alzheimer’s disease and those who have either Parkinson’s disease with dementia or dementia with Lewy bodies.

In contrast, CSF levels of alpha-synuclein were lower in patients with certain dementias than in control subjects, but not to a degree that would assist in differential diagnosis, the investigators said.

They assessed the prognostic accuracy of the panel of five protein biomarkers in CSF samples from 107 healthy control subjects and 346 patients who were treated for parkinsonism and/or dementia at two university hospitals in Sweden. A newly developed assay allowed the simultaneous quantification of levels of alpha-synuclein, Abeta 1-42, T-tau, and P-tau in the CSF samples. Neurofilament light chain (NF-L) protein was assessed from the same samples using a conventional ELISA (enzyme-linked immunosorbent assay).

The study subjects were diagnosed as having Parkinson’s disease (90 patients), Alzheimer’s disease (48 patients), Parkinson’s disease with dementia (33 patients), dementia with Lewy bodies (70 patients), progressive supranuclear palsy (45 patients), multiple system atrophy (48 patients), or corticobasal degeneration (12 patients).

"Most important, we found that the diagnostic accuracy of a panel of 5 biomarkers representing tau-, beta-amyloid-, and alpha-synuclein pathology was high enough to be of clear value in the clinical work-up of differentiating patients with Alzheimer’s disease from those with Parkinson’s disease with dementia and dementia with Lewy bodies," Dr. Hall and her colleagues wrote (Arch. Neurol. 2012 Aug. 27 [doi:10.1001/archneurol.2012.1654]).

The five-marker panel had 90% sensitivity and 81% specificity for differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with dementia. It differentiated Alzheimer’s disease from dementia with Lewy bodies alone with 88% sensitivity and 81% specificity.

The investigators found that the panel could discriminate Parkinson’s disease from atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy) with 85% sensitivity and 92% specificity.

"Our study [also] confirmed that the CSF levels of NF-L are increased in atypical parkinsonian disorders, and the observed diagnostic accuracy of NF-L is high enough to be clinically relevant," they added.

Higher levels of NF-L, but not of the other biomarkers, correlated with more severe disease in patients who had Parkinson’s disease, progressive supranuclear palsy, and Alzheimer’s disease, "which might reflect an increase in axonal pathology over time in these patients," Dr. Hall and her associates wrote.

This study was supported by the Swedish Research Council, the Swedish Alzheimer Foundation, the Torsten and Ragnar Soderberg Foundation, the Swedish Brain Power Consortium, Lund University, and Sahlgrenska Academy. No financial conflicts of interest were reported.

Next Article: