MAPT and early-onset autosomal dominant Alzheimer disease: Reactive neuronal hypertrophy in the hippocampal CA1 region has been shown in Alzheimer’s disease subjects prior to symptom onset62 supporting early regional volume increases, either as a cellular response to amyloid and tau deposition, or a compensatory process prior to degeneration of neurons and synapses.63 Future work combining MRI-based volumetric analysis and design-based stereology, similar to studies in transgenic mice,64,65 would help fill critical gaps in knowledge regarding mechanisms underlying pathological morphometric change in the TgF344-AD model.