A recently developed HMGB1-specific mAb blocking the TLR4-binding epitope of HMGB1 has demonstrated beneficial therapeutic effects in mouse models of preclinical Alzheimer ́s disease [46,91], and other neutralizing anti-HMGB1 mAbs exerted neuroprotection in a rat model of Parkinson ́s disease [89]. This evidence concerns the gene TLR4 and Alzheimer disease.