The observed apoB/phospho-tau association in pre-symptomatic AD is markedly modulated by the presence of the APOE-ε4 allele but not by the passage of peripheral apoB into the CNS [74]; supporting the notion that the total cholesterol could act more as a surrogate biomarker for APOE-ε4 mediated effects than a direct player in the pathophysiological process. The gene discussed is APOE; the disease is Alzheimer disease.