As 63% (279/436) of ADNC + individuals also had substantial TDP-43 proteinopathy, CAA, or both, it is possible that more than half of individuals given this ‘gold-standard’ diagnosis of Alzheimer’s disease within this population may actually have suffered cognitive decline equally driven by these underappreciated co-pathological mechanisms. The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.