Contactin-2 is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and its levels in AD brains inversely correlate with BACE1 levels and amyloid plaque density [44] suggesting that an increase in BACE1 activity observed in late-onset AD [45–49] results in increased contactin-2 cleavage. Here, BACE1 is linked to Alzheimer disease.