Several studies have investigated SM metabolism in Alzheimer’s disease [reviewed in Bienias et al. (2016)], and one of these studies found that inhibiting nSMase2 in APP/PS1 mice leads to a reduction in the number of EVs in the brain and serum, a reduction in amyloid-β-42 concentration in plaques, and decreased levels of most Cer species in the serum (Dinkins et al., 2014). The gene discussed is SMPD3; the disease is early-onset autosomal dominant Alzheimer disease.