Our findings that inheritance of two APOE ε4 alleles is associated with smaller neurons in both epilepsy and Alzheimer’s disease, but not in neurologically normal controls, together with the dramatic elevation of markers of stress in APOE ε4,4 carriers, suggests that such individuals are at greater risk of neuronal damage, regardless of the initiating injury. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.