Plasma Aβ as a biomarker for predicting Aβ-PET status in Alzheimer’s disease：a systematic review with meta-analysis

Abstract

ObjectiveAmyloid-β positron emission tomography (Aβ-PET) scan has been proposed to detect amyloid-β (Aβ) deposition in the brain. However, this approach is costly and not ideal for the early diagnosis of Alzheimer’s disease. Blood-based Aβ measurement offers a scalable alternative to the costly or invasive biomarkers. The aim of this study was to statistically validate whether plasma Aβ could predict Aβ-PET status via meta-analysis.MethodsWe systematically searched for eligible studies from PubMed, Embase and Cochrane Library, which reported plasma Aβ levels of amyloid-β positron emission tomography-positive (PET (+)) and amyloid-β positron emission tomography-negative (PET (−)) subjects. We generated pooled estimates using random effects meta-analyses. For any study that has significant heterogeneity, metaregression and subgroup analysis were further conducted. Publication bias was appraised by funnel plots and Egger’s test.Results16 studies with 3047 participants were included in the meta-analysis. Among all the enrolled studies, 10 studies reported plasma Aβ40 values, while 9 studies reported plasma Aβ42 values and 13 studies reported Aβ42/Aβ40 ratio. The pooled standardised mean difference (SMD) was 0.76 (95% CI −0.61 to 2.14, p=0.28) in the plasma Aβ40 values group. Plasma Aβ42 values group has a pooled SMD of −0.60 (95% CI −0.80 to −0.41, p<0.0001). In the plasma Aβ42/Aβ40 ratio group, the pooled SMD was −1.44 (95% CI −2.17 to −0.72, p<0.0001).ConclusionPlasma Aβ40 values might not distinguish between PET (+) and PET (−) people. However, plasma Aβ42 values and plasma Aβ42/Aβ40 ratio could be served as independent biomarkers for predicting Aβ-PET status.

Associations of plasma phosphorylated tau181 and neurofilament light chain with brain amyloid burden and cognition in objectively defined subtle cognitive decline patients

“…3,4 The core blood biomarkers of AD include Aβ42 (or Aβ42/40 ratio), phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and total tau (Ttau), which reflect Aβ pathology, tau pathology, and neuronal damage, respectively. 5,6 Various experimental results have shown that lower plasma Aβ42/Aβ40 ratio was associated with higher amyloid cortical burden, 7,8 faster Aβ accumulation rates, 9 greater cognitive declines, 10,11 and increased risk of developing AD dementia at follow-up. 12 Other research suggested plasma p-tau181 reflected changes in hyperphosphorylated tau in the brain in Aβ+ individuals.…”

“…Various experimental results have shown that lower plasma Aβ42/Aβ40 ratio was associated with higher amyloid cortical burden, 7 , 8 faster Aβ accumulation rates, 9 greater cognitive declines, 10 , 11 and increased risk of developing AD dementia at follow‐up. 12 Other research suggested plasma p‐tau181 reflected changes in hyperphosphorylated tau in the brain in Aβ+ individuals.…”

Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer’s disease

“…Many previous studies have shown that plasma biomarkers could predict disease stage and that integrating multiple plasma biomarkers could improve prediction accuracy ( Palmqvist et al, 2021 ; West et al, 2021 ; Cheng et al, 2022 ). In the present study, we investigated the prediction ability for disease stages of integrating plasma and urine biomarkers compared to using plasma biomarkers alone, revealing that combining all biomarkers could improve prediction accuracy.…”

Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?

“…found that Aβ oligomerization was significantly higher in AD patients than in normal people. Plus, the high correlations between Aβ oligomerization levels and other AD biomarkers, such as phosphorylated tau protein (pTau), amyloid positron emission tomography (PET) imaging, CSF biomarkers for Aβ42, total tau, and brain magnetic resonance imaging (MRI) were confirmed in many studies (Choi et al, 2021;Cheng et al, 2022).…”

“…To reduce the amount of lab workload and accelerate the SILK studies, Mawuenyega et al (2013) developed an efficient and specific quantitative isoform characterization and kinetics method. Plenty of studies adopting the IP-MS method elucidated that plasma Aβ42 concentration and Aβ42/Aβ40 rate are promising biomarkers for predicting Aβ status in individuals (Portelius et al, 2006(Portelius et al, , 2015Ovod et al, 2017;Cheng et al, 2022). Furthermore, immunoprecipitation together with SampleStream mass spectrometry (SampleStream-MS) was established.…”