Constitutive α- and β-secretase cleavages of the amyloid precursor protein are partially coupled in neurons, but not in frequently used cell lines

► A potential inverse coupling of ADAM10 and BACE1-cleavage of APP was investigated. ► Constitutive ADAM10 and BACE1 cleavages of APP were largely uncoupled in cell lines. ► In neurons BACE1 inhibition increased ADAM10 cleavage of APP. ► In contrast, knock-out of ADAM10 did not increase BACE1-cleavage or Aβ levels. ► Thus, ADAM10/BACE1 cleavage are partially coupled in neurons, but not in cell lines.