The amyloid beta 42/38 ratio as a plasma biomarker of early memory deficits in cognitively unimpaired older adults.

The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aβ peptides individually and the Aβ42/40 ratio, but not the Aβ42/38 ratio, were significantly correlated with brain amyloid (Aβ-PET). Multiple linear modeling, adjusting for age, sex, education, APOE4 and Aβ-PET showed significant associations between the Aβ42/38 ratio and memory. Further, associations between the Aβ42/38 ratio and learning scores were stronger in males and in Aβ-PET-negative individuals. In contrast, no significant associations were detected between the Aβ42/40 ratio and any learning measure. These studies implicate the Aβ42/38 ratio as a biomarker to assess early memory deficits and underscore the utility of the Aβ38 fragment as an important biomarker in the AD field.