These observations might be at least partly explained by the role that Aβ itself appears to play in HSP since a recent study has demonstrated that soluble, secreted Aβ, but not the parent protein APP nor other APP cleavage products, mediates the homeostatic upscaling of synaptic strength following TTX treatment in cultured neurons (Galanis et al., 2021). This evidence concerns the gene APP and hereditary spastic paraplegia.