Given the significant upregulation of A1R signaling and notable tau phosphorylation have also been observed in Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS),[42, 43, 44, 45] we propose that this vicious cycle mechanism mediated by tau pathology and A1R signaling may extend beyond HSD and AD models, influencing the pathological mechanisms in various neurodegenerative disorders. Here, MAPT is linked to amyotrophic lateral sclerosis.