Cerebrospinal fluid neurogranin as a new player in prion disease diagnosis and prognosis

Abstract

Neurogranin (Ng) and its role as Alzheimer’s disease (AD) biomarker: Ng is a calmodulin-binding protein mainly expressed in cerebral structures such as the cortex, hippocampus and striatum. It is mainly located in the dendritic processes, particularly in post-synaptic compartments, but also in the cytosolic compartment, being likely involved in the regulation of the intracellular calcium-calmodulin signaling pathway (Represa et al., 1990). In the last decade, a plethora of studies have demonstrated that cerebrospinal fluid (CSF) Ng is increased in AD patients and in individuals with an ADlike CSF profile (Kester et al., 2015a). This increase seems to be disease-specific because other neurodegenerative conditions including frontotemporal dementia, Lewy body dementia, Parkinson’s disease, progressive supranuclear palsy, multiple system atrophy or Huntington’s disease, present CSF Ng concentrations similar to controls (Wellington et al., 2016). Ng levels in CSF appear to be elevated in mild cognitive impairment (MCI)-affected individuals who progress to AD and are highly related to memory and cognitive function (Kester et al., 2015a; Tarawneh et al., 2016), which indicates that this protein may serve as an early AD biomarker with diagnostic utility in pre-dementia disease stages, and with prognostic utility to predict cognitive decline and MCI-to-AD conversion.