Hyperphosphorylation of tau protein in superficial CNS siderosis

Abstract

In superficial CNS siderosis chronic subarachnoidal hemorrhage leads to hemosiderin deposits in the subpial layers of the brain and spinal cord. Many years usually pass between the initial event causing chronic bleedings and the development of cerebellar ataxia, sensory hearing loss and various sensorimotor deficits. The only therapeutic option is to identify and eliminate the bleeding source. Otherwise slow relentless decline to a bedridden state and dementia is usually unavoidable. However, it is not known how precisely leptomeningeal hemosiderin deposits induce progressive neurodegeneration. Here we present the first report of a patient with superficial CNS siderosis in whom cerebrospinal fluid biomarkers of brain damage were assessed. Levels of neurofilament light protein, glial fibrillary acidic protein, total tau protein and, most importantly, hyperphosphorylated tau protein were increased. The results indicate that in superficial CNS siderosis neurodegeneration may be secondary to iron toxicity and oxidative stress. Similar mechanisms have been suggested for other neurodegenerative disorders such as Alzheimer's disease.