Advances in blood-based protein biomarkers for Alzheimer's disease

Clark, Lorraine F.; Kodadek, Thomas

doi:10.1186/alzrt172

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…Blood-based biomarkers may be an attractive option, but those available from among plasma proteins or lipids still need higher sensitivity and specificity. Measuring membrane proteins in blood cell samples may open a new avenue in this regard [3] .…”

Section: Introductionmentioning

confidence: 99%

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients

Várady

Szabó

Fehér

et al. 2015

Alz & Dem Diag Ass & Dis Mo

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Preventive measures, prognosis, or selected therapy in multifactorial maladies, including Alzheimer's disease (AD), require the application of a wide range of diagnostic assays. There is a large unmet need for relatively simple, blood-based biomarkers in this regard. We have recently developed a rapid and reliable flow cytometry and antibody-based method for the quantitative measurement of various red blood cell (RBC) membrane proteins from a drop of blood. Here, we document that the RBC expression of certain membrane proteins, especially that of the GLUT1 transporter and the insulin receptor (INSR), is significantly higher in AD patients than in age-matched healthy subjects. The observed differences may reflect long-term metabolic alterations relevant in the development of AD. These findings may pave the way for a diagnostic application of RBC membrane proteins as relatively stable and easily accessible personalized biomarkers in AD.

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Section: Introductionmentioning

confidence: 99%

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients

Várady

Szabó

Fehér

et al. 2015

Alz & Dem Diag Ass & Dis Mo

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Section: Discussionmentioning

confidence: 99%

“…The advantages of OASIS, particularly the low levels of nonspecific binding, led us to conclude that OASIS should feature fewer false negatives in a diagnostic assay that measured biomarkers of neurodegeneration. Given the high stability of antibodies and relatively easy accessibility of peripheral blood samples, 59 we conducted measurements of autoantibodies raised against PD-associated αS species in both PD and HC plasma. Surprisingly, we observed a consistently low background in measurements of plasma autoantibodies recognizing αS oligomers displayed on-matrix, which is illustrated in the results of our plasma anti-αS detection experiment (Figure 4).…”

Section: ■ Discussionmentioning

confidence: 99%

Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of α-Synuclein Autoantibodies in Human Plasma

Yang

Bouchard

et al. 2022

Bioconjugate Chem.

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The misfolding and subsequent aggregation of amyloidogenic proteins is a classic pathological hallmark of neurodegenerative diseases. Aggregates of the α-synuclein protein (αS) are implicated in Parkinson's disease (PD) pathogenesis, and naturally occurring autoantibodies to these aggregates are proposed to be potential early-stage biomarkers to facilitate the diagnosis of PD. However, upon misfolding, αS forms a multitude of quaternary structures of varying functions that are unstable ex vivo. Thus, when used as a capture agent in enzyme-linked immunosorbent assays (ELISAs), significant variance among laboratories has prevented the development of these valuable diagnostic tests. We reasoned that those conflicting results arise due to the high nonspecific binding and amyloid nucleation that are typical of ELISA platforms. In this work, we describe a multiplexed, easy-to-operate immunoassay that is generally applicable to quantify the levels of amyloid proteins and their binding partners, named Oxaziridine-Assisted Solid-phase Immunosorbent (OASIS) assay. The assay is built on a hydrophilic poly(ethylene glycol) scaffold that inhibits aggregate nucleation, which we show reduces assay variance when compared to similar ELISA measurements. To validate our OASIS assay in patient-derived samples, we measured the levels of naturally occurring antibodies against the αS monomer and oligomers in a cohort of donor plasma from patients diagnosed with PD. Using OASIS assays, we observed significantly higher titers of immunoglobulin G antibody recognizing αS oligomers in PD patients compared to those in healthy controls, while there was no significant difference in naturally occurring antibodies against the αS monomer. In addition to its development into a blood test to potentially predict or monitor PD, we anticipate that the OASIS assay will be of high utility for studies aimed at understanding protein misfolding, its pathology and symptomology in PD, and other neurodegenerative diseases.

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“…Thus, there has been much research effort to identify reliable biomarkers for AD [ 9 ] . Compared to biomarkers that require brain imaging and collection of the cerebrospinal fluid (CSF), the blood-based biomarkers are particularly desirable because they are less expensive, relatively non-invasive, and easily accessible [ 10 , 11 ] . Through the search of such blood-derived biomarkers, some auto-antibodies have emerged as potentially effective bio-markers for AD ( Table 1 ).…”

Section: Autoantibodies As Potential Biomarkers For Admentioning

confidence: 99%

Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications

Wu¹,

L²

2016

J Biomed Res

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Alzheimer’s disease (AD) is a prevalent and debilitating neurodegenerative disorder in the elderly. The etiology of AD has not been fully defined and currently there is no cure for this devastating disease. Compelling evidence suggests that the immune system plays a critical role in the pathophysiology of AD. Autoantibodies against a variety of molecules have been associated with AD. The roles of these autoantibodies in AD, however, are not well understood. This review attempts to summarize recent findings on these autoantibodies and explore their potential as diagnostic/ prognostic biomarkers for AD, their roles in the pathogenesis of AD, and their implications in the development of effective immunotherapies for AD.

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Advances in blood-based protein biomarkers for Alzheimer's disease

Cited by 8 publications

References 52 publications

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients

Chemoselective Bioconjugation of Amyloidogenic Protein Antigens to PEGylated Microspheres Enables Detection of α-Synuclein Autoantibodies in Human Plasma

Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications

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