Of note, cognitively normal patients with either AD-associated risk markers (e.g., T-tau, p-tau, and Aβ42 levels in the CSF) or the APOE4 allele showed elevated CSF levels of the MMP-3/Tissue inhibitor of metalloproteinase 1 (TIMP-1) ratio compared to counterparts without risk factors [97]. Here, TIMP1 is linked to Alzheimer disease.