Evaluation of Plasma Aβ as Predictor of Alzheimer's Disease in Older Individuals Without Dementia: A Population-Based Study

Abstract

Amyloid-β (Aβ) pathology is a major component in the mechanisms behind Alzheimer's disease (AD). Measurement of Aβ(42) in cerebrospinal fluid predicts cognitive decline in patients with mild cognitive impairment and identifies AD in patients with dementia. However, studies on Aβ in plasma are contradictory. In this prospective population-based study, plasma Aβ(42) and Aβ(40) were measured at baseline in 730 adults aged 70 years or older and without dementia. After five years, plasma levels were analyzed again and participants were assessed for development of dementia. During follow-up, 53 individuals (7%) developed dementia of which 37 (5%) were classified as AD. No difference in baseline plasma Aβ(42), Aβ(40), or Aβ(42)/Aβ(40) ratio levels were observed between converters to dementia or AD compared to the cognitively stable individuals. However, individuals with plasma Aβ(40) levels above the median level for the group at baseline had an increased risk of developing dementia and AD during the follow-up, even after adjustment for age, gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence interval = 1.0-4.7, p < 0.05). Neither plasma Aβ(42) nor the Aβ(42)/Aβ(40) ratio influenced the risk of developing dementia or AD. Moreover, Aβ(42) and Aβ(40) levels increased over the 5 years, whereas the Aβ(42)/Aβ(40) ratio decreased (p < 0.001). In conclusion, this study suggests that measurement of plasma Aβ should not be used clinically to predict dementia or AD. However, plasma Aβ(40) may possibly be regarded as a moderate risk marker comparable to other risk markers for AD such as first-degree family history of dementia.

Plasma amyloid beta measurements - a desired but elusive Alzheimer's disease biomarker

“…The study of Okereke et al [64] found that a decrease in Aβ 1-42 /Aβ 1-40 in the repeated plasma measurement was associated with greater cognitive decline. Lastly, studies reported by Hansson et al [29] and Toledo et al [10] found that during follow-up of 324 subjects for 5 years in the former and 613 subjects for 2 to 3 years in the latter study, there was an increase of Aβ 1-40 and Aβ 1-42 , whereas Aβ 1-42 /Aβ 1-40 decreased.…”

“…Different measures of plasma Aβ have been associated with progression to dementia (Table 4): high baseline Aβ 1-42 [30,57], low baseline Aβ 1-42 /Aβ 1-40 [58,59], low baseline Aβ 1-40 or Aβ 1-42 [60], high baseline Aβ 1-40 [29], high Aβ 1-40 or low Aβ 1-42 /Aβ 1-40 [61] and low Aβ 1-40 in older subjects [62]. Finally, other studies found no associations of plasma Aβ levels with progression to dementia [10,13,63].…”

“…A small number of studies have included repeated sampling of plasma Aβ levels [10,27,29,57]. In the study by Mayeux et al [27], a general increase was found for plasma Aβ 1-40 over time, and plasma Aβ 1-40 levels in CN stable subjects showed an increase over time, while incident and baseline AD subjects showed a decrease over time.…”

Plasma amyloid‐β and risk of Alzheimer's disease in the Framingham Heart Study

“…Using the same selection of prospective cohorts, we first extracted hazard ratios of incident AD or dementia and their 95% confidence intervals from minimally adjusted models comparing lowest versus highest quantiles (quartiles or tertiles) of plasma Aβ 1-42 levels, plasma Aβ 1-40 levels or plasma Aβ 1-42 /Aβ 1-40 ratio. In addition to our results and those published by Shah et al [15], and Lui et al [12], we contacted three previously published studies, including Shah et al, that had measured plasma Aβ levels, to obtain unpublished hazard ratios [13, 15, 30]. Lastly, we performed fixed- and random-effect meta-analyses, and evaluated heterogeneity using the I 2 measure.…”

Plasma and cerebrospinal fluid amyloid-β levels in late-life depression: A systematic review and meta-analysis

“…Reduced CSF Aβ 42 levels is associated with an increased risk of progression of mild cognitive impairment (MCI) to AD (Diniz et al, 2008). Previous clinico and epidemiological studies have reported that increased Aβ 42 levels and lower plasma Aβ 42 :Aβ 40 ratio can be an indicator of a higher risk of progression from MCI to AD; though other studies have also found no association between plasma Aβ biomarkers and increased risk of progression (Hansson et al, 2012; Fei et al, 2011; Koyama et al , 2012; Gabelle et al, 2013). Previous studies investigated the levels of Aβ peptides in the CSF and plasma of LLD patients.…”