Phosphoneurofilament heavy chain and vascular endothelial growth factor as cerebrospinal fluid biomarkers for ALS.

To cite this article: Margarida Gonçalves, Mamede De Carvalho, Cristina Peixoto, Paula Alves, Carmo Barreto, Abel Oliva, Susana Pinto, Ana Laborinho-Pronto, Marta Gromicho & Júlia Costa (2016): Phosphoneurofilament heavy chain and vascular endothelial growth factor as cerebrospinal fluid biomarkers for ALS, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, DOI: 10.1080/21678421.2016.1212894


Introduction
The most promising molecular markers for ALS are neurofilaments, namely phosphorylated neurofilament heavy chain (pNFH). In ALS, increased level of pNFH has been reported in the CSF (1,2), in particular in fast progressors (3), with a negative correlation with disease duration (4).
VEGF has been associated with ALS pathogenesis (5). Decreased levels were described in the CSF and plasma of ALS patients (6), but the results are inconsistent (1).
Here we explore the diagnostic potential of combining pNFH and VEGF as ALS biomarker.

Population and methods
Groups of 36 ALS patients with probable or definite disease (revised El Escorial criteria) and 15 patients with other neurological disorders were studied (Table I). All patients gave written consent; the protocol was approved by the ethics committee.
Statistical analysis was performed using GraphPad Prism 6.

Discussion
We have observed that pNFH levels were increased in the CSF and correlated with the rate of disease progression and disease duration, which is in agreement with other reports (1-3). Concerning diagnostic specificity and sensitivity our values are slightly lower than those reported elsewhere (2), which might be due to the different populations analysed and number of subjects. On the other hand, in agreement with others (6) we observed a lower level of VEGF in ALS CSF.
To our knowledge pNFH and VEGF are not interdependent; however, we have explored the diagnostic value of combining both biomarkers, both abnormal in ALS (1,2,6). We found that this index has a potentially higher diagnostic accuracy than the single evaluation of pNFH. Higher CSF pNFH/VEGF ratio was associated with a more aggressive disease course and respiratory failure, probably explained by the combination of rapid motor neurons death and deregulation in the synthesis of VEGF in ALS.
Our results underscore the potential of CSF pNFH as a diagnostic and prognostic biomarker in ALS and combined analysis of pNFH/VEGF could provide higher diagnostic yield. This should be investigated in a larger population of patients.
Supplementary material for this article is available via the supplementary tab on the article's online page at http://dx.doi.org/10.1080/21678421.2016. 1212894.