Chen Y, Huang X, Zhang YW, Rockenstein E, Bu G, Golde TE, Masliah E, Xu H.
Alzheimer's β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid.
J Neurosci. 2012 Aug 15;32(33):11390-5.
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One of the most vexing issues in elucidating the molecular pathogenesis of AD has been the challenge of working out whether there exist neurotoxic pathways that act independently of the genesis of amyloid-β oligomers.
Such pathways have been identified for presenilins, and now Xu et al. suggest that overactivation of BACE might also fall into this category.
This dovetails with recent evidence from Giuseppina Tesco indicating that persistent activation of BACE might occur as a consequence of traumatic brain injury (Walker et al., 2012). This would dovetail with the neuropathology of chronic traumatic encephalopathy, which includes tauopathy but little or no amyloidosis. Long-term studies of mice overexpressing both BACE and human tau might shed light on this question. In any event, the data from Xu et al. indicate that BACE has many important targets other than APP.