Wang et al. further reported mitochondrial fragmentation and ultrastructural damage in the brain of CRND8 APP transgenic mice by both confocal microscopy and electron microscopy studies, accompanying mitochondrial functional deficits at 3 months of age, well before any noticeable amyloid deposition, which suggest that mitochondrial dynamic abnormalities occur early in the course of AD-related changes [109]. Here, APP is linked to Alzheimer disease.