Unlike Aβ, tau, α-synuclein, and huntingtin proteins aggregate principally within neurons and glia.38,39 However, in vitro and in vivo evidence suggest that pathogenic aggregates of these proteins are actively secreted into the ISF and this secretion may contribute to the intracellular transmission and spread of pathology across brain regions in AD, PD, and HD.33,40 The degree to which communication between the ISF, CSF, and the activity of mural cells contributes to the concentration and spread of protein aggregates throughout disease progression is an area of active research in neurofluids. This evidence concerns the gene HTT and Huntington disease.