Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer’s disease

INTRODUCTION: Synaptic dysfunction and degeneration are early fundamental pathophysiological characteristics of Alzheimer's disease (AD). In addition, synaptic depletion closely correlates with clinical disease severity. Biomarkers that may track synaptic dysfunction in AD are eagerly awaited. Areas covered: Here, we reviewed the significance of the post-synaptic protein neurogranin - particularly enriched in dendritic spines - as a biomarker of early synaptic dysfunction in AD. We also examined its role as a marker to predict disease progression. Expert commentary: Current evidence indicates that neurogranin may serve as a mechanism-of-action biomarker aiding the in vivo investigation of AD-related pathophysiological pathways. Its use may support the development of targeted therapeutic interventions tailored to the individual patient, i.e. 'molecularly' targeted therapies, according to the evolving precision medicine paradigm.