TLR4 and Down syndrome: However, equally as important, sleep disordered breathing and associated IH is also severe in >50% of patients with other major health problems including ischemic (e.g. stroke), traumatic (e.g. spinal injury), neurodegenerative (e.g. Alzheimer's, Parkinson's, ALS, MS) and genetic neural disorders (e.g. Down's syndrome, Fragile X) [56], [57], [58], [59], [60], [61], [62]._ENREF_27 IH triggers the upregulation of endogenous TLR4 ligands in the CNS [34], and we find that TLR4 expression is upregulated in microglia by IH.