Figure 1.

A large body of evidence suggests that the dominant effect of human apoE isoforms on AD risk is to shift the onset of disease via alterations in the probability of amyloid deposition, likely during the preclinical, asymptomatic phase. Consistent with this hypothesis, individuals appear to accumulate amyloid in the order ε4 > ε3 > ε2, well before AD clinical symptomology becomes manifest (Figure adapted from Holtzman, DM 2008 Nature, 454(7203):418–20)¹⁷¹.