ACAN and Alzheimer disease: There is increasing evidence from rodent AD models and post‐mortem human brain tissue studies, that PNNs are extensively disrupted in AD [154]; however, aggrecan, one key component of the PNN matrix, is present in human dense‐core Aβ plaques (perhaps as a neuroprotective mechanism), and consequently, it has been shown in human cortical and subcortical AD brain tissue, that neurons associated with aggrecan‐based PNNs are somehow resistant to tau pathology [151].