COG133 is a peptide fragment of ApoE that corresponds to residues 133-149 of the ApoE LDL receptor-binding domain and an antagonist of α7 nicotinic acetylcholine receptors (nAChRs; IC = 720 nM). It suppresses TNF-α and nitric oxide (NO) release in BV-2 microglia when used at concentrations ranging from 10 to 50 µM. In vivo, COG133 reduces LPS-induced increases in brain levels of TNF-α and IL-6 in mice. It decreases hippocampal neuronal degeneration and the latency to find the platform in the Morris water maze in a mouse model of closed head injury induced by surgical midline impact when administered at doses of 203 and 406 µg/kg. COG133 (1 mg/kg) also delays disease onset and reduces disease severity in a mouse model of experimental autoimmune encephalomyelitis (EAE).