New players in old amyloid precursor protein-processing pathways

The amyloid precursor protein (APP) gives rise to β‐amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease (AD) patients. The generation of β‐amyloid peptides requires the enzymatic activity of the β‐site APP‐cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by neurons and increased BACE1 protein concentrations and enzymatic activities have been reported in the brains of AD patients. However, there is accumulating evidence that, in addition to neurons, reactive astrocytes are capable of expressing BACE1 and, therefore, may contribute to β‐amyloid plaque formation. This suggests that conditions accompanied by chronic astrocyte activation may contribute to developing AD.