2010
DOI: 10.1523/jneurosci.5180-09.2010
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Blood-Borne Amyloid-β Dimer Correlates with Clinical Markers of Alzheimer's Disease

Abstract: Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-␤ (A␤) plaques and tau neurofibrillary tangles. A␤ processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While A␤ deposition is the most prominent feature of AD, oligomeric forms of A␤ have been implicated as the toxic species inducing the neuronal dysfunction. C… Show more

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Cited by 68 publications
(58 citation statements)
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“…A further complication is that although some antibodies may recognize conformations of Aβ oligomers with greater affinity than they recognize Aβ monomers, the relative concentrations of npg r e v i e w oligomers and monomers may still make such tools unsuitable for detecting oligomeric species from fluids such as CSF from patients with Alzheimer's disease. It is probable that a combination of technologies, such as immune capture with mass spectrometry, will be needed to obtain the resolution needed to perform these studies 89 .…”
Section: An Alternative Interpretation Of Ab Oligomer Toxicitymentioning
confidence: 99%
“…A further complication is that although some antibodies may recognize conformations of Aβ oligomers with greater affinity than they recognize Aβ monomers, the relative concentrations of npg r e v i e w oligomers and monomers may still make such tools unsuitable for detecting oligomeric species from fluids such as CSF from patients with Alzheimer's disease. It is probable that a combination of technologies, such as immune capture with mass spectrometry, will be needed to obtain the resolution needed to perform these studies 89 .…”
Section: An Alternative Interpretation Of Ab Oligomer Toxicitymentioning
confidence: 99%
“…From the interstitial compartment or brain parenchyma, soluble Ab monomers and oligomers may enter into the CSF compartment (Englund et al 2009;Fukumoto et al 2010) and even the peripheral blood circulation (Roher et al 2009;Xia et al 2009). Although much more work is required to establish the existence of blood-borne Ab oligomers and confirm their cerebral origin, there is preliminary evidence that blood dimer levels may correlate with clinical features of AD (Villemagne et al 2010; see also Blennow et al 2011). Interestingly, such blood-borne dimers are associated with blood cellular membranes (mainly white cells and platelets) and may increase as the natural history of AD advances (Villemagne et al 2010).…”
Section: Tissue-and Cell-derived Natural Oligomersmentioning
confidence: 99%
“…Although much more work is required to establish the existence of blood-borne Ab oligomers and confirm their cerebral origin, there is preliminary evidence that blood dimer levels may correlate with clinical features of AD (Villemagne et al 2010; see also Blennow et al 2011). Interestingly, such blood-borne dimers are associated with blood cellular membranes (mainly white cells and platelets) and may increase as the natural history of AD advances (Villemagne et al 2010). In contrast, levels of Ab42 monomers in both the CSF and plasma are generally considered to fall as AD progresses (Lui et al 2010a;Blennow et al 2011).…”
Section: Tissue-and Cell-derived Natural Oligomersmentioning
confidence: 99%
“…The recent report that a Phase 3 trial of the Aβ-specific monoclonal antibody solanezumab produced a small but significant cognitive benefit in patients with mild AD (Doody, 2012) has made it even more critical to understand the earliest changes in the economy of synaptotoxic Aβ oligomers in the brain and biological fluids. A few reports of the detection of apparent Aβ oligomers in CSF and plasma have appeared (Fukumoto et al, 2010; Gao et al, 2010; Klyubin et al, 2008; Villemagne et al, 2010); however, the interpretation of these reports has been clouded by failure to define the precise oligomeric unit the assays are detecting, an inability to exclude definitively the detection of Aβ monomers, and in some cases, the lack of validating the assays on natural oligomers in biological samples.…”
Section: Introductionmentioning
confidence: 99%