Objectives: Determine whether (1) a relationship exists between plasma amyloid-β (Aβ)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 Aβ peptide levels differ between apolipoprotein E
(APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aβ 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 Aβ1-40 and 1-42 were quantified using
ELISA. Results: Wave1 plasma levels of Aβ peptides and Aβ1−42/1-40 ratio were lower in aMCI and AD, and Aβ1−42
was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities.
The relationships of Aβ1-40 and Aβ1-42 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 Aβ1−42
and the ratio measure. Conclusion: 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.
Keywords: Aβ1-40, Aβ1-42, APOE, brain volume, cognition, neuropsychological test, MRI, plasma, white matter hyperintensities.
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