A better understanding of axon versus dendrite APP and Aβ is important. DeBoer and colleagues show that APP is significantly more present at the surface of the plasma membrane of axons while it is more in the inside of dendrites. Using constructs to target APP to axons or dendrites, they then present interesting and novel results consistent with more Aβ secretion from dendrites than axons. They also show further evidence for little Aβ17-40 (p3) production by neurons, which is not fully appreciated in the field, since many still describe the α-secretase pathway with p3 generation as the main or normal APP cleavage pathway. Further, DeBoer et al. show more evidence that rodents generate particularly abundant Aβ11-40 peptides from rodent APP compared to those from human APP, which (in the presence of with rodent BACE1) makes mostly Aβ1-40 peptides. It still remains unclear clear how much Aβ 1-x versus 11-x peptides are generated from human APP in human neurons. Overall, this is very carefully done study from an experienced lab that adds important information in elucidating the biology of neuronal APP and Aβ.
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Lund University
A better understanding of axon versus dendrite APP and Aβ is important. DeBoer and colleagues show that APP is significantly more present at the surface of the plasma membrane of axons while it is more in the inside of dendrites. Using constructs to target APP to axons or dendrites, they then present interesting and novel results consistent with more Aβ secretion from dendrites than axons. They also show further evidence for little Aβ17-40 (p3) production by neurons, which is not fully appreciated in the field, since many still describe the α-secretase pathway with p3 generation as the main or normal APP cleavage pathway. Further, DeBoer et al. show more evidence that rodents generate particularly abundant Aβ11-40 peptides from rodent APP compared to those from human APP, which (in the presence of with rodent BACE1) makes mostly Aβ1-40 peptides. It still remains unclear clear how much Aβ 1-x versus 11-x peptides are generated from human APP in human neurons. Overall, this is very carefully done study from an experienced lab that adds important information in elucidating the biology of neuronal APP and Aβ.
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