Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca<sup>2+</sup> release in neurons.<h4>Results</h4>Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Here, RYR2 is linked to early-onset autosomal dominant Alzheimer disease.