01873nas a2200193   4500008004100000245017900041210006900220260000800289300001300297490000600310520111700316100002101433700002001454700002001474700001801494700002501512700002501537856011701562       2018                        eng d00aAdvanced glycation end products modulate amyloidogenic APP processing and tau phosphorylation: a mechanistic link between glycation and the development of alzheimer's disease0 aAdvanced glycation end products modulate amyloidogenic APP proce  cMAY  a988-10000 v93 aAdvanced glycation end products (AGEs) are implicated in the pathology of Alzheimer's disease (AD), as they induce neurodegeneration following interaction with the receptor for AGE (RAGE). This study aimed to establish a mechanistic link between AGE-RAGE signaling and AD pathology. AGE-induced changes in the neuro2a proteome were monitored by SWATH-MS. Western blotting and cell-based reporter assays were used to investigate AGE-RAGE regulated APP processing and tau phosphorylation in primary cortical neurons. Selected protein expression was validated in brain samples affected by AD. The AGE-RAGE axis altered proteome included increased expression of cathepsin B and asparagine endopeptidase (AEP), which mediated an increase in A beta(1-)(42) formation and tau phosphorylation, respectively. Elevated cathepsin B, AEP, RAGE, and pTau levels were found in human AD brain, coincident with enhanced AGEs. This study demonstrates that the AGE-RAGE axis regulates A beta(1-)(42) formation and tau phosphorylation via increased cathepsin B and AEP, providing a new molecular link between AGEs and AD pathology.1 aBatkulwar, Kedar1 aGodbole, Rashmi1 aBanarjee, Reema1 aKassaar, Omar1 aWilliams, Robert, J.1 aKulkarni, Mahesh, J.  uhttps://library.ncl.res.in/content/advanced-glycation-end-products-modulate-amyloidogenic-app-processing-and-tau