Dataset Information

Electrochemical Detection of Plasma Immunoglobulin as a Biomarker for Alzheimer's Disease.

ABSTRACT: The clinical diagnosis and treatment of Alzheimer's disease (AD) represent a challenge to clinicians due to the variability of clinical symptomatology as well as the unavailability of reliable diagnostic tests. In this study, the development of a novel electrochemical assay and its potential to detect peripheral blood biomarkers to diagnose AD using plasma immunoglobulins is investigated. The immunosensor employs a gold electrode as the immobilizing substrate, albumin depleted plasma immunoglobulin as the biomarker, and polyclonal rabbit Anti-human immunoglobulin (against IgA, IgG, IgM) as the receptor for plasma conjugation. The assay showed good response, sensitivity and reproducibility in differentiating plasma immunoglobulin from AD and control subjects down to 10-9 dilutions of plasma immunoglobulin representing plasma content concentrations in the pg mL-1 range. The newly developed assay is highly sensitive, less time consuming, easy to handle, can be easily modified to detect other dementia-related biomarkers in blood samples, and can be easily integrated into portable devices.

SUBMITTER: Garyfallou GZ

PROVIDER: S-EPMC5713623 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Electrochemical Detection of Plasma Immunoglobulin as a Biomarker for Alzheimer's Disease.

Garyfallou Goulielmos-Zois GZ Ketebu Orlando O Şahin Samet S Mukaetova-Ladinska Elizabeta B EB Catt Michael M Yu Eileen Hao EH

Sensors (Basel, Switzerland) 20171027 11

The clinical diagnosis and treatment of Alzheimer's disease (AD) represent a challenge to clinicians due to the variability of clinical symptomatology as well as the unavailability of reliable diagnostic tests. In this study, the development of a novel electrochemical assay and its potential to detect peripheral blood biomarkers to diagnose AD using plasma immunoglobulins is investigated. The immunosensor employs a gold electrode as the immobilizing substrate, albumin depleted plasma immunoglobu ...[more]

PMID: 29077013

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Project description:The quantification of phosphorylated tau in biofluids, either cerebrospinal fluid (CSF) or plasma, has shown great promise in detecting Alzheimer's disease (AD) pathophysiology. Tau phosphorylated at threonine 231 (p-tau231) is one such biomarker in CSF but its usefulness as a blood biomarker is currently unknown. Here, we developed an ultrasensitive Single molecule array (Simoa) for the quantification of plasma p-tau231 which was validated in four independent cohorts (n = 588) in different settings, including the full AD continuum and non-AD neurodegenerative disorders. Plasma p-tau231 was able to identify patients with AD and differentiate them from amyloid-β negative cognitively unimpaired (CU) older adults with high accuracy (AUC = 0.92-0.94). Plasma p-tau231 also distinguished AD patients from patients with non-AD neurodegenerative disorders (AUC = 0.93), as well as from amyloid-β negative MCI patients (AUC = 0.89). In a neuropathology cohort, plasma p-tau231 in samples taken on avergae 4.2 years prior to post-mortem very accurately identified AD neuropathology in comparison to non-AD neurodegenerative disorders (AUC = 0.99), this is despite all patients being given an AD dementia diagnosis during life. Plasma p-tau231 was highly correlated with CSF p-tau231, tau pathology as assessed by [18F]MK-6240 positron emission tomography (PET), and brain amyloidosis by [18F]AZD469 PET. Remarkably, the inflection point of plasma p-tau231, increasing as a function of continuous [18F]AZD469 amyloid-β PET standardized uptake value ratio, was shown to be earlier than standard thresholds of amyloid-β PET positivity and the increase of plasma p-tau181. Furthermore, plasma p-tau231 was significantly increased in amyloid-β PET quartiles 2-4, whereas CSF p-tau217 and plasma p-tau181 increased only at quartiles 3-4 and 4, respectively. Finally, plasma p-tau231 differentiated individuals across the entire Braak stage spectrum, including Braak staging from Braak 0 through Braak I-II, which was not observed for plasma p-tau181. To conclude, this novel plasma p-tau231 assay identifies the clinical stages of AD and neuropathology equally well as plasma p-tau181, but increases earlier, already with subtle amyloid-β deposition, prior to the threshold for amyloid-β PET positivity has been attained, and also in response to early brain tau deposition. Thus, plasma p-tau231 is a promising novel biomarker of emerging AD pathology with the potential to facilitate clinical trials to identify vulnerable populations below PET threshold of amyloid-β positivity or apparent entorhinal tau deposition.

Dataset Information

Electrochemical Detection of Plasma Immunoglobulin as a Biomarker for Alzheimer's Disease.

Publications

Electrochemical Detection of Plasma Immunoglobulin as a Biomarker for Alzheimer's Disease.

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