Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by abnormal cerebrospinal fluid (CSF) flow and consequent cerebral ventricular enlargement due to imbalance of CSF production and absorption. The typical triad symptoms, namely cognitive decline, gait disturbance, and urinary incontinence, are thought to be caused by disruption of CSF circulation. However, some patients may still experience symptomatic progression after functional shunting, suggesting that iNPH is far more complicated than a simple disorder of CSF circulation. Moreover, the diagnostic workup of iNPH can be challenging due to symptomatic and neuroimaging overlaps with other neurological disorders, such as Alzheimer’s disease. Furthermore, accumulating studies indicate that the pathogenesis of iNPH might relate to multiple mechanisms, including abnormalities of brain development, brain extracellular matrix, synaptic function, blood flow, and cerebral metabolism. Therefore, iNPH is not an isolated entity in occurrence and development. Nevertheless, different pathogeneses may result in protein content changes in CSF, and the biomarkers in CSF may reflect the possible mechanisms involving the etiology of iNPH and are potentially useful in assisting the diagnosis and treatment selection. In this review, we summarize the main findings of CSF biomarkers and aim to outline a possible synthetic profile in assisting iNPH diagnosis and therapeutic options.