Limited cleavage of tau with matrix-metalloproteinase MMP-9, but not MMP-3, enhances tau oligomer formation

► We investigated the effect of limited proteolytic cleavage on tau oligomer formation. ► MMP-3/-9, which are elevated in AD and PSP, generate specific tau cleavage products. ► Tau fragments were characterized by SDS-PAGE and mass spectroscopy. ► Limited cleavage by MMP-9 promotes tau oligomer formation detected by FCS and SIFT. ► Extracellular proteases such as MMP-9 may thus contribute to tau pathology.