Spinal fluid biomarker research – PSP v. MSA v. PD, and which PDers will develop LBD?

There was an interesting – but hard to understand (at least for me!) – paper published a couple of weeks ago in JAMA Neurology, an important journal.  A lot of the worldwide research community is focused on biomarkers.  If we could give someone a blood test (or a spinal tap, in the case of this paper) to determine if the person had PD, PSP, or MSA, that would be groundbreaking.  And it might be helpful to know which of those who have PD will eventually develop dementia (or Lewy Body Dementia in particular).

In this paper, Swedish researchers looked at cerebrospinal fluid (CSF) of 128 people with Parkinson’s Disease (PD), Progressive Supranuclear Palsy (PSP), and Multiple System Atrophy (MSA) over a 5-9 year period.  None of the 128 had dementia.  CSF of 30 older healthy controls was also examined.

Here’s an (understandable) excerpt from a useful summary of the paper on Alzforum, posted last Friday:

“Scientists…report a combination of useful candidates in the cerebrospinal fluid (CSF) that may help [differentiate these diseases and predict who will decline cognitively]. One biomarker in particular, neurofilament light chain (NFL), a neuronal cytoskeleton protein, best distinguished PSP from PD. In helping predict which patients with PD would become demented, NFL joined two other proteins: Aβ42 and heart fatty acid–binding protein (HFABP), which helps carry fatty acids to the mitochondria for oxidization. All in all, the results propose useful diagnostic biomarkers for these diseases and may offer clues to their pathophysiology. … No single biomarker or combination separated MSA from PD.”

In the study, 35 percent of the PD patients developed dementia over the five to nine years of participation.  This seemed to be a high conversion rate to dementia for John Growdon, a neurologist at Mass General in Boston.  He said:

“‘To be able to predict with some certainty who’s on the path to dementia and who’s not is a very important finding,’ he told Alzforum. If these results can be reproduced, it could mean that Aβ-lowering therapeutics for Alzheimer’s disease (AD) will be applicable to the PDD group. It would be useful to compare these biomarkers in other disorders that might also cause diagnostic confusion, such as AD and dementia with Lewy bodies, he said.”

For what it’s worth, Dr. Growdon described this as a “very important study.”

Here’s a link to the Alzforum post, if you’d like to read more:


I’ve copied the abstract below.




JAMA Neurology. 2015 Aug 10.

Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease.
Bäckström DC, Eriksson Domellöf M, Linder J, Olsson B, Öhrfelt A, Trupp M, Zetterberg H, Blennow K, Forsgren L.

Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies.

To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders.

Design, Setting, and Participants:
Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by a movement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison.

Main Outcomes and Measures:
Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria.

Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders.

Conclusions and Relevance:
The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein were related to future PDD, providing new insights into the etiology of PDD.

PubMed ID#:  26258692