Studies have demonstrated higher concentrations of CSF Ng in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients, possibly indicating synaptic injury or dysfunction, and a correlation between Ng concentration and progression of cognitive decline.17 30 One of these studies30 found intra-individual levels of Ng to not increase in later stages of MCI or AD, but in cognitively normal adults, which could indicate that increased Ng concentrations reflect presymptomatic injury or dysfunction to the synapse. Here, NRGN is linked to early-onset autosomal dominant Alzheimer disease.