Furthermore, there was no reduction in infarct volume or improvement in functional outcome when TNF inhibitors were delivered by i.c.v. administration, even though the concentrations of the inhibitors in brain tissue were sufficient to neutralize TNF and potentially promote neuroprotection as demonstrated in previous studies using animal models of Alzheimer’s disease (MacPherson et al., 2017). Here, TNF is linked to early-onset autosomal dominant Alzheimer disease.