Transient increase in CSF GAP-43 concentration after ischemic stroke

BackgroundCerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer's disease patients; however, patients suffering from stroke have not been studied previously.MethodsThe concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0-1, 2-4, 7-9, 3weeks, and 3-5months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.ResultsIncreased GAP-43 concentration was detected from day 7-9 to 3weeks after stroke, compared to day 1-4 and to levels in the control group (P=0.02 and P=0.007). At 3-5months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (r(s)=0.65, P=0.001).ConclusionsThe transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer's disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.