Therefore, IgM anti-NMDAR1 autoantibodies may provide a feasible early prevention against excitotoxicity from stroke or traumatic brain injury where the BBB is disrupted, long-lasting neuroprotection in Alzheimer’s disease where the BBB may be compromised, and cognitive enhancement in schizophrenia and other psychiatric disorders where a baseline level of the IgM autoantibodies crossovering the BBB may be beneficial. The gene discussed is CD40LG; the disease is early-onset autosomal dominant Alzheimer disease.