Figure 1.
Amyloid-β secretion in AD neurons. In early-onset AD, mutations AβPP, PS1, and PS2 genes activate β- and γ-secretases, cleave Aβ. In late-onset AD, oxidative stress related factors (O2•, H2O2, OH), risk factors including ApoE4, sortilin related receptor 1, clusterin, and complement component either activate secretases or decrease Aβ clearance in AD neurons. The cleaved Aβ accumulate in subcellular compartments, including mitochondria, endoplasmic reticulum, Golgi-network, lysosomes, and multivesicular bodies, and disrupt the functions of these subcellular organelles and damage neuronal function.