Biomarker Breakthrough

A multi-center collaborative study has just been published in the journal JAMA Neurology. Sponsored by the Michael J. Fox Foundation’s Parkinson’s Progression Markers Initiative, the researchers measured four proteins in the cerebrospinal fluid (CSF) of early, untreated Parkinson’s patients compared to healthy controls. The four proteins are alpha-synuclein, two types of tau, and beta-amyloid—of Alzheimer disease  fame.

The study showed a reduction in each of four proteins between PD patients and controls. However the difference measured is still too small to be used as a practical diagnostic test. What the study does provide is the first evidence for a biological basis for different types of Parkinson disease. Measurement of CSF proteins were shown to distinguish between PD patients with postural instability-gait disturbance-dominant and tremor-dominant PD.

So why is this important if it can’t be used currently to make a diagnosis?

  • First, it will further researcher’s efforts to define the biological basis for the disease.
  • It would also enable researchers to more accurately group patients for assessment of treatment protocols. In any research protocol—especially drug trials—one wants to compare apples to apples, lest a positive outcome be diluted out and overlooked.
  • It could point the way toward recognition of PD before the appearance of overt symptoms (by which time 70% of the dopamine cells are already lost). This would provide a window for earlier, more specific treatment opportunities once they become available.

I was particularly excited to see continued evidence for the role of tau in PD. With support from the American Parkinson Disease Association, I had published the first evidence of an association of PD with tau (Lazzarini, et al. 1997); (Golbe, et al. 2001).  Fourteen years later, a genome-wide association study continued to support a strong association with the MAPT/tau locus (Spencer, et al. 2011). The current study lends further credence to  a biological role for tau in PD.

References:

Golbe, Lawrence I., et al. 2001
The tau A0 allele in Parkinson’s disease. Movement Disorders 16(3):442-447.

Lazzarini, A.M. , et al.1997   
Tau intronic polymorphism in Parkinson’s Disease and Progressive Supranuclear Palsy. Neurology 48:A427.

Spencer, C. C., et al. 2011
Dissection of the genetics of Parkinson’s disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21. Hum Mol Genet 20(2):345-53.

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