FN1 and Alzheimer disease: During human aging, brain ECM alters in composition [37]; this also occurs in the AD brain, where CSPGs are upregulated around amyloid plaques, abnormal collagen IV and fibronectin deposition occurs, and there is a loss of perineuronal nets (protective ECM structures) around neurons (see 33 for an excellent review of additional biomechanic changes in the AD brain).