Plasma Levels Investigated as Alzheimer's Disease Biomarkers

Plasma levels of Aβ1-40 and 1-42 were quantified using enzyme-linked immunosorbent assay (ELISA). Plasma levels of the two peptides and the Aβ1-42/1-40 ratio were lower in aMCI and Alzheimer's disease than in cognitively normal controls, and lower levels of Aβ1-42 were associated with lower global cognition and hippocampal volume and higher levels of white matter hyperintensities, which are believed to contribute to Alzheimer's disease.

A genetic component was also identified, with associations between Aβ1-40 and cognitive and brain volume measures predominantly observed in individuals carrying the ε4 allele, while the opposite was observed in non-carriers. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aβ1-42 and the ratio measure. The relationships of Aβ1-40 and Aβ1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively.

The authors concluded that Plasma Aβ levels and the Aβ1−42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Aβ1-40 and Aβ1-42 in ε4 carriers and non-carriers. These data support the Aβ sink model of AD pathology, and suggest that plasma Aβ measures may serve as biomarkers of AD. Anne Poljak, PhD, the lead author of the study, said, “While Aβ has traditionally been measured using cerebrospinal fluid, plasma presents a more accessible sample for routine collection and screening although results to date have been variable.” The study was published on April 18, 2016, in the journal Current Alzheimer Research.

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