If WML are invariably used as a surrogate biomarker for SVD, as suggested by current clinical guidelines [16, 22], this will bias cohort stratification in clinical trials, result in misdiagnosis of patients, and have a detrimental impact on the choice of therapeutic interventions, e.g. AD patients being misdiagnosed with VaD would not receive acetylcholinesterase inhibitors as recommended for managing mild to moderate AD [18]. The gene discussed is ACHE; the disease is Alzheimer disease.