RESUMEN
OBJECTIVES: Determine whether (1) a relationship exists between plasma amyloid-ß (Aß)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Aß peptide levels differ between apolipoprotein E (APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aß levels. METHODS: Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE ε4 genotyped. Plasma levels of Aß1-40 and 1-42 were quantified using ELISA. RESULTS: Wave1 plasma levels of Aß peptides and Aß1-42/1-40 ratio were lower in aMCI and AD, and Aß1-42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities. The relationships of Aß1-40 and Aß1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aß1-42 and the ratio measure. CONCLUSION: Plasma Aß levels and the Aß1-42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Aß1-40 and Aß1-42 in ε4 carriers and non-carriers. These data support the Aß sink model of AD pathology, and suggest that plasma Aß measures may serve as biomarkers of AD.
