Moreover, endocytosis mediated by APPL1/Rab5 constitutes a novel APP-dependent pathogenic pathway in Alzheimer’s disease (AD) (Kim et al., 2016) and APPL1 has also been found to accumulate as granules around neurons in postmortern human brain of AD (Ogawa et al., 2013). This evidence concerns the gene RAB5A and early-onset autosomal dominant Alzheimer disease.