A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer’s disease

Shanthi, Keerthanaa Balasubramanian; Krishnan, Sreeram; Rani, P.

doi:10.1177/2050312115598250

Cited by 28 publications

(22 citation statements)

References 55 publications

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“…Because authors of previous meta-analyses have not found any significant difference between the total plasma Aβ 40 and Aβ 42 levels in patients with AD and control individuals [ 19 – 24 ], detecting crude oligomeric Aβ in plasma was a challenge, owing to its low concentrations in the blood, especially in the midst of several interfering factors at high concentrations. Aβ autoantibodies, albumin, fibrinogen, immunoglobulin, apolipoprotein J, ApoE, transthyretin, α-2-macroglobulin, serum amyloid P component, plasminogen, and amylin [ 19 – 23 ] could interfere with the detection of oligomeric Aβ by MDS.…”

Section: Discussionmentioning

confidence: 99%

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

et al. 2017

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BackgroundSoluble amyloid-β (Aβ) oligomers are the major toxic substances associated with the pathology of Alzheimer’s disease (AD). The ability to measure Aβ oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring Aβ oligomers selectively, was used to detect Aβ oligomers in the plasma of patients with AD and healthy control individuals.MethodsTwenty-four patients with AD and 37 cognitively normal control individuals underwent extensive clinical evaluations as follows: blood sampling; detailed neuropsychological tests; brain magnetic resonance imaging; cerebrospinal fluid (CSF) measurement of Aβ42, phosphorylated tau protein (pTau), and total tau protein (tTau); and 11C-Pittsburgh compound B (PIB) positron emission tomography. Pearson’s correlation analyses between the estimations of Aβ oligomer levels by MDS and other conventional AD biomarkers (CSF Aβ42, pTau, and tTau, as well as PIB standardized uptake value ratio [PIB SUVR]) were conducted. ROC analyses were used to compare the diagnostic performance of each biomarker.ResultsThe plasma levels of Aβ oligomers by MDS were higher in patients with AD than in normal control individuals, and they correlated well with conventional AD biomarkers (levels of Aβ oligomers by MDS vs. CSF Aβ42, r = −0.443; PIB SUVR, r = 0.430; CSF pTau, r = 0.530; CSF tTau, r = 0.604). The sensitivity and specificity of detecting plasma Aβ oligomers by MDS for differentiating AD from the normal controls were 78.3% and 86.5%, respectively. The AUC for plasma Aβ oligomers by MDS was 0.844, which was not significantly different from the AUC of other biomarkers (p = 0.250).ConclusionsPlasma levels of Aβ oligomers could be assessed using MDS, which might be a simple, noninvasive, and accessible assay for evaluating brain amyloid deposition related to AD pathology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0324-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

et al. 2017

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“…Nevertheless, decline of the plasma Aβ42/Aβ40 ratio has been reported in some studies, while others have reported the opposite result, or no difference 10 . A recent meta-analysis showed that the level of plasma Aβ42 did not vary significantly between AD patients and controls and cannot serve as a reliable marker for the diagnosis of AD 12 . There are several potential causes of contradictory measurements of plasma Aβ levels.…”

Section: Introductionmentioning

confidence: 99%

Plasma Aβ analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder

Hsiao

Chen

et al. 2018

Sci Rep

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An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer’s disease (AD); however, the usefulness of plasma Aβ levels are not well-established. This study investigated the relationships between plasma Aβ levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent 18F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aβ40 and Aβ42. We found inverse associations of the plasma Aβ42 level and the Aβ42/Aβ40 ratio, and a positive association of the plasma Aβ40 level, with cerebral amyloid deposition in the precuneus, parietal and posterior cingulate cortex. Subgroup analyses in subjects with higher 18F-florbetapir uptake values or MDD with amnestic mild cognitive impairment revealed more pervasive relationships of plasma Aβ measures with 18F-florbetapir binding across the brain regions examined. The study suggested that regional brain amyloid deposition in terms of 18F-florbetapir PET uptake had weak-to-moderate associations with plasma Aβ42 and Aβ40 levels, and the Aβ42/Aβ40 ratio. Validation in a larger population of subjects of known cerebral amyloidosis status is needed. Careful interpretation of plasma data is warranted.

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“…In our study, the plasma Aβ 42 level did not show a correlation with the questionnaire score and could not distinguish CCDS dogs from normal dogs. In AD studies, results for the use of plasma Aβ 42 as a biomarker have been controversial [35]. The expression was in contrast with that reported in a previous study, which showed that plasma Aβ was signi cantly gradually decreased in early CCDS and severe CCDS, while the highest Aβ 42 plasma level was observed in younger dogs [7,34].…”

Section: Discussionmentioning

confidence: 69%

“…Even though many candidate biomarkers have been identi ed in both blood and cerebrospinal uid (CSF), none of these markers has been used routinely in the clinic. In previous studies, plasma Aβ 42 was evaluated as a biomarker in AD and CCDS, but it is highly variable and seems to be controversial [7,34,35]. Therefore, the identi cation and characterization of novel biomarkers are necessary for the reliable diagnosis of CCDS.…”

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confidence: 99%

The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

Phochantachinda¹,

Chantong²,

Reamtong³

et al. 2020

Preprint

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Background: Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification.Results: Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 45 and 52 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p = 0.125, R2 = 0.27).Conclusions: Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis.

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A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer’s disease

Cited by 28 publications

References 55 publications

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

Plasma Aβ analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder

The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

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A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer’s disease

Cited by 28 publications

References 55 publications

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease

Plasma Aβ analysis using magnetically-labeled immunoassays and PET 18F-florbetapir binding in non-demented patients with major depressive disorder

The Plasma Amyloid Beta 42&nbsp;(Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

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The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand