Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Abstract

Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Abeta as an AD biomarker and its relationship with Abeta load and to determine the effect of different assay methods on the interpretation of Abeta levels. Plasma Abeta1-40, Abeta1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Abeta levels were compared to Abeta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Abeta1-42 and Abeta1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Abeta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Abeta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Abeta has diagnostic value in a panel of biomarkers.

Serum concentration of beta amyloid peptide and the activity of angiotensin converting enzyme in alzheimers disease patients: search for a potential biomarker

“…Our results does not affirm those studies that show an increase in Aβ 42 and/or Aβ 40 in plasma of AD patients [26][27] and is in line with those that report decreases in Aβ 42 and Aβ 40 in plasma of AD patients compared with non-AD demented individuals and controls. [28][29][30][31] Data in Figure 3, about the concentration ratios of Aβ 42 to Aβ 40 , shows that the ratio does not change significantly when compared to control samples (Figure 3a), and also the differences are not significant when the effect of aging was studied in either males (Figure 3b) or females (Figure 3c). Generally, it seems that Aβ 42 /Aβ 40 could not be considered as either a diagnostic or prognostic indicator.…”

“…26,27 Decrease in Aβ 42 and/or the ratio of Aβ 42 /Aβ 40 in plasma of AD patients compared with non-AD demented individuals and controls has also been reported. [28][29][30][31] According to some studies it seems that a low level of Aβ42/Aβ40 ratio is associated with AD and generally with dementias. 26 On the other hand, most prospective studies indicate that elevation in plasma Aβ 42 level is present before or just at the onset of a clinically diagnosed disease.…”

Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment

“…6 In a multisite study, increased PiB cortical binding was associated with low plasma A␤42 and A␤42/40 levels across a diagnostically heterogenous sample of AD, MCI, and control subjects but not within each diagnostic group. 11 These studies were confounded by highly variable plasma A␤ values, undetectable plasma A␤ values in several subjects in one study, 6 and the use of multiple assays for plasma A␤ within each study. 11 Plasma A␤ levels are approximately onehundredth of CSF A␤ levels, leading to difficulties in accurate measurement.…”

“…11 These studies were confounded by highly variable plasma A␤ values, undetectable plasma A␤ values in several subjects in one study, 6 and the use of multiple assays for plasma A␤ within each study. 11 Plasma A␤ levels are approximately onehundredth of CSF A␤ levels, leading to difficulties in accurate measurement.…”

Blood Biomarkers for Alzheimer’s Disease: Much Promise, Cautious Progress

“…Aβ42 is present at very low concentrations in plasma, it is prone to plasma protein binding and may be eliminated by enzyme activity. These factors may explain why plasma Aβ42 does not correlate well with the CSF profile [ 25,26,27,28 ] and there are mixed reports of inverse correlation [ 29 ] and of lack of correlation [ 30 ] of plasma Aβ42 with amyloid PET. Further problems with plasma Aβ42 are its susceptibility to technical factors such as aliquot volume and delay to freezing samples [ 31 ].…”