APP and Alzheimer disease: Besides olfactory dysfunction, ApoE4 was shown to exacerbate AD-related pathology by (i) increasing β pathway processing of full-length APP and, therefore, Aβ production; (ii) decreasing astrocyte- and microglia-mediated Aβ clearance; (iii) reducing neuroprotective Sirtuin T1 expression; (iv) inducing mitochondrial dysfunction and lysosomal leakage; (v) triggering Tau and APP phosphorylation; (vi) inhibiting insulin signaling; and (vii) inducing programmed cell death [23, 153, 176].