TIMP2 is expressed in cells of the periphery, contributing to high levels in the plasma16, and also in hippocampal neurons26, with expression in both compartments declining with age16. Interestingly, Timp2 has been shown to be upregulated in subpopulations of microglia in response to aging and AD pathology as part of a panel of genes termed the disease-associated microglia (DAM) profile29. To explore its expression within microglia, we noted its enriched transcript abundance within microglia in published transcriptomic atlases, including in Tabula Muris Senis30, and in the Allen Brain Cell scRNAseq and MERFISH Atlas31, in which Timp2 is expressed at high levels in the brain, particularly in hippocampal microglia (Supplementary Fig. 1a–c), though it is also expressed in cortical and striatal microglia (Supplementary Fig. 1d–g). To begin to characterize whether microglia express TIMP2 at the protein level and how its loss influences function at early stages, we isolated primary microglia from early postnatal (P5-P8) forebrain from wild-type (WT) and TIMP2 knockout (KO) mice (Fig. 1a) at an age when global TIMP2 levels are high16. We find high levels of TIMP2 protein by both immunoblotting of primary microglia lysates and immunocytochemistry (ICC), whereas TIMP2 was not detected in TIMP2 KO microglia (Fig...

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