FIGURE 3.
Working models of olfactory deficit arising in the olfactory epithelium in mouse models of Alzheimer’s disease. Top, Overexpression of mutated human amyloid precursor protein (hAPP) induces an upregulation of γ-secretase complex, leading to the production of different types of Aβ peptides (Cheng et al., 2011, 2016; Kim et al., 2018). Amyloid-β 40/42 (Aβ40/42) causes axonal mistargeting of olfactory receptor neurons (ORNs) in the olfactory bulb (OB) (Cao et al., 2012b), whereas Aβ56 causes ORN apoptosis (Kim et al., 2018). Middle, Mutation of tau also causes ORN apoptosis. Bottom, Apolipoprotein E deficiency alters the maturation of ORNs. All these alterations lead to deficits in olfactory-driven behaviors (Nathan et al., 2010; Zhang et al., 2018).