The Relationship Between Plasma Aβ Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study

Author(s): 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 , Perminder S. Sachdev .

Journal Name: Current Alzheimer Research

Volume 13 , Issue 3 , 2016

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Abstract:

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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Article Details

VOLUME: 13
ISSUE: 3
Year: 2016
Page: [243 - 255]
Pages: 13
DOI: 10.2174/1567205013666151218150202
Price: $58

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