APP and Alzheimer disease: With decades of intensive studies of AD etiologies, it is generally believed that AD is not a homogeneous condition but a group of heterogeneous disease with potential causes and risks ranging from mutations (APP, PS1, and PS2), genetic risks (e.g., APOE4), aging, inflammation, senescence, compromised autophagy/mitophagy, damaged mitochondria, and defective alternative splicing events (ASEs) (4–7).