Cerebrospinal fluid biomarkers of infantile congenital hydrocephalusReport as inadecuate

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Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid CSF in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus CHC to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value.


CSF levels of amyloid precursor protein APP and derivative isoforms sAPPα, sAPPβ, Aβ42, tau, phosphorylated tau pTau, L1CAM, NCAM-1, aquaporin 4 AQP4, and total protein TP were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC.


CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age p<0.0001 and AUC = 0.99, followed by normalized sAPPβ p = 0.0001, AUC = 0.95, tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC odds ratio = 528, sensitivity = 0.94, specificity = 0.97; these infants were 32 times more likely to have CHC.


CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.

Author: David D. Limbrick Jr., Brandon Baksh, Clinton D. Morgan, Gakwaya Habiyaremye, James P. McAllister II, Terrie E. Inder, Deanna Mer

Source: http://plos.srce.hr/


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