Biofunctionalized Magnetic Nanoparticles for Specifically Detecting Biomarkers of Alzheimer’s Disease in Vitro

Alzheimer’s disease (AD) is the most common form of dementia. The development of assay technologies able to diagnose early-stage AD is important. Blood tests to detect biomarkers, such as amyloid and total Tau protein, are among the most promising diagnostic methods due to their low cost, low risk, and ease of operation. However, such biomarkers in blood occur at extremely low levels and are difficult to detect precisely. In the early 2000s, a highly sensitive assay technology, immunomagnetic reduction (IMR), was developed. IMR involves the use of antibody-functionalized magnetic nanoparticles dispersed in aqueous solution. The concentrations of detected molecules are converted to reductions in the ac magnetic susceptibility of this reagent due to the association between the magnetic nanoparticles and molecules. To achieve ultra-high sensitivity, a high-Tc superconducting-quantum-interference-device (SQUID) ac magnetosusceptometer was designed and applied to detect the tiny reduction in the ac magnetic susceptibility of the reagent. Currently, a 36-channeled high-Tc SQUID-based ac magnetosusceptometer is available. Using the reagent and this analyzer, extremely low concentrations of amyloid and total Tau protein in human plasma could be detected. Further, the feasibility of identifying subjects in early-stage AD via assaying plasma amyloid and total Tau protein is demonstrated. The results show a diagnostic accuracy for prodromal AD higher than 80% and reveal the possibility of screening for early-stage AD using SQUID-based IMR.

show abstract

“…[70]. Interference with the assay is partly caused by non-specific binding between antibodies and non-target molecules.…”

Section: Discussionmentioning

confidence: 99%

Detection of Plasma Biomarkers Using Immunomagnetic Reduction: A Promising Method for the Early Diagnosis of Alzheimer’s Disease

Yang¹,

Chiu

Chen

et al. 2017

Neurol Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the diagnosis of BPSD is challenging in DS because of the underlying intellectual disabilities, and the assessment of BPSD in DS has not been well studied (Dekker et al, 2015; Prasher et al, 2015). We have developed a new technology called immunomagnetic reduction (IMR), which is capable of assaying molecules at very low concentrations (Yang et al, 2011; Chiu et al, 2012, 2013, 2014). IMR measures the reduction in the alternating-current magnetic susceptibility of suspended bio-magnetic nanoparticles owing to the immunospecific conjugation between the nanoparticles and Aβ peptides and tau proteins.…”

Section: Introductionmentioning

confidence: 99%

Blood Beta-Amyloid and Tau in Down Syndrome: A Comparison with Alzheimer’s Disease

Lee

Yang²,

Chieh

et al. 2017

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

Background: Changes in β-amyloids (Aβ) and tau proteins have been noted in patients with Alzheimer’s disease (AD) and patients with both Down syndrome (DS) and AD. However, reports of changes in the early stage of regression, such as behavioral and psychological symptoms of dementia (BPSD), in DS are sparse.Methods: Seventy-eight controls, 62 patients with AD, 35 with DS and 16 with DS with degeneration (DS_D), including 9 with BPSD and 7 with dementia, were enrolled. The levels of β-amyloids 40 and 42 (Aβ-40, Aβ-42) and tau protein in the blood were analyzed using immunomagnetic reduction (IMR). The Adaptive Behavior Dementia Questionnaire (ABDQ) was used to evaluate the clinical status of the degeneration.Results: The Aβ-40 and tau levels were higher and the Aβ-42 level and Aβ-42/Aβ-40 ratio were lower in DS than in the controls (all p < 0.001). Decreased Aβ-40 and increased Aβ-42 levels and Aβ-42/40 ratios were observed in DS_D compared with DS without degeneration (all p < 0.001). The ABDQ score was negatively correlated with the Aβ-40 level (ρ = −0.556) and the tau protein level (ρ = −0.410) and positively associated with the Aβ-42 level (ρ = 0.621) and the Aβ-42/40 ratio (ρ = 0.544; all p < 0.05).Conclusions: The Aβ-40 and Aβ-42 levels and the Aβ-42/Aβ-40 ratio are considered possible biomarkers for the early detection of degeneration in DS. The elevated Aβ-40 and tau levels in DS may indicate early neurodegeneration. The increased Aβ-42 in DS_D may reflect the neurotoxicity of Aβ-42. The paradox of the tau decreases in DS_D could be explained by a burnout phenomenon during long-term neurodegeneration. The different patterns of the plasma beta amyloids and tau protein may imply a different pathogenesis between DS with degeneration and AD in the general population, in spite of their common key pathological features.

show abstract

“…12 In such an assay, the sensing unit consists of two excitation coils and one pickup coil. Excitation currents with frequencies f 1 and f 2 are separately applied to the excitation coils and the change of ac susceptibility is then analyzed at a target frequency of f 1 þ 2f 2 , to qualitatively characterize the abundance of vascular endothelial growth factors (VEGFs), 14,15 chloramphenicol extracted from shrimp, 16 biomarkers expressed in Alzheimer's disease, 17 human C-reactive protein (CRP), 7,13 alpha-fetoprotein, 18 and nervous necrosis virus extracted from groupers. 19 In this work, a platform is developed for assaying biomolecules by using single frequency ac susceptometor.…”

mentioning

confidence: 99%

Time-dependent phase lag of biofunctionalized magnetic nanoparticles conjugated with biotargets studied with alternating current magnetic susceptometor for liquid phase immunoassays

et al. 2013

View full text Add to dashboard Cite

show abstract

Biofunctionalized Magnetic Nanoparticles for Specifically Detecting Biomarkers of Alzheimer’s Disease in Vitro

Cited by 107 publications

References 24 publications

Detection of Plasma Biomarkers Using Immunomagnetic Reduction: A Promising Method for the Early Diagnosis of Alzheimer’s Disease

Detection of Plasma Biomarkers Using Immunomagnetic Reduction: A Promising Method for the Early Diagnosis of Alzheimer’s Disease

Blood Beta-Amyloid and Tau in Down Syndrome: A Comparison with Alzheimer’s Disease

Time-dependent phase lag of biofunctionalized magnetic nanoparticles conjugated with biotargets studied with alternating current magnetic susceptometor for liquid phase immunoassays

Contact Info

Product

Resources

About