Anne Poljak, John D. Crawford, George A. Smythe, Henry Brodaty, Melissa J. Slavin, Nicole A. Kochan, Julian N. Trollor, Wei Wen, Karen A. Mather, Amelia A. Assareh, Pek C. Ng and Perminder S. Sachdev Pages 243 - 255 ( 13 )
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.
Aβ1-40, Aβ1-42, APOE, brain volume, cognition, neuropsychological test, MRI, plasma, white matter hyperintensities.
Bioanalytical Mass Spectrometry Facility, School of Medical Sciences, University of New South Wales, Sydney, Australia.