Intracellular localization of AβPP and Aβ. AβPP is synthesised in the endoplasmic reticulum (ER) and is trafficked through Golgi network (G), to the cell surface or to mitochondria (Mt). In the plasma membrane the apolipoprotein (Apo) receptor LRP1 forms a complex with AβPP, inducing the internalization of the amyloid precursor protein, together with other plasma membrane enzymes, such as the β-secretase BACE and the γ-secretase presenilin (PS): Aβ is produced through amyloidogenic cleavage of AβPP. The plasma membrane complex AβPP with another Apo receptor, LRP1B, decreases the cellular uptake of AβPP. Sources of mitochondrial Aβ are the endosome (En) but also G and ER. G production of Aβ is decreased by binding of AβPP to another Apo receptor SorLA that blocks AβPP in the early G, counteracting AβPP cleavage pathways. Aβ enters into the mitochondrial matrix through TOM and translocase of the inner membrane (TIM) or is derived from mitochondria-associated AβPP metabolism. N = nucleus, OMM = outer mitochondrial membrane, IMM = inner mitochondrial membrane.
