APP and early-onset autosomal dominant Alzheimer disease: For the CNS, the importance of amyloid β generation and its multiplex interactions with the ECM are highlighted by studies showing that the ECM regulates APP levels in fibroblasts and neuronal cells (Bronfman et al., 1996), amyloid β induces ECM degradation in rat astrocytes (Deb et al., 2003) and that both fibrillar and oligomeric forms of amyloid β associate with proteins present at synapses, a characteristic closely related to synapse loss and neurodegeneration observed in Alzheimer’s disease (Selkoe, 2000; Spires-Jones and Hyman, 2014).