Figure 6. Proposed model for the expression profile of endogenous Aβ oligomers in human brain tissue.

We analyzed human brain tissue from 158 subjects with ages of 1 to 98 years at the time of death. Two cohorts were used for this study (Lesne et al., under review): 49 brain samples were from healthy subjects (from 1 to 62 years) and 89 from subjects with preclinical AD, MCI or AD. Briefly our findings indicate that in healthy subjects Aβ*56 was first detected in the 5^th decade of life preceding elevations in Aβ trimers and dimers observed in the 6^th and 7^th decades. In preclinical AD, Aβ*56 appeared to reach a plateau. In MCI brains, Aβ*56 levels decreased significantly while Aβ trimers levels rose sharply. At this stage, brain levels of Aβ dimers slowly elevated. One possible explanation for this change in the relative expression of these species might be due to a destabilization of the non-fibrillar oligomerization pathway in favor of the fibrillar oligomerization pathway. Finally in AD brain tissue, Aβ dimers were increased while levels of Aβ*56 and Aβ trimers fell to discrete amounts. Such proposed scenario must need to be tested in longitudinal studies.