New Assay for Old Markers-Plasma Beta Amyloid of Mild Cognitive Impairment and Alzheimer's Disease

Chiu, Ming‐Jang; Yang, Shieh‐Yueh; Chen, T. F.; Chieh, Jen Jie; Huang, Tao; Yip, Ping K.; Yang, Hong-Chang; Cheng, Teng-Hu; Chen, Y. F.; Hua, Mau‐Sun; Horng, Herng-Er

doi:10.2174/156720512804142967

Cited by 68 publications

(59 citation statements)

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“…A 60-μl aliquot of plasma was mixed with 60 μl of reagent at room temperature for determination of the tau protein concentration. The underlying mechanism and the technological details of the immunomagnetic reduction assay are described in our previous reports (Chiu et al, 2012; Yang et al, 2013). …”

Section: Methodsmentioning

confidence: 97%

Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults

Chiu

Fan

Chen

et al. 2017

Front. Aging Neurosci.

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Using an ultra-sensitive technique, an immunomagnetic reduction assay, the plasma tau level can be measured to a limit of quantification of pg/ml. In total 126 cognitively normal middle-aged and older adults (45–95 years old) were recruited. The plasma tau levels were significantly higher in the older group (aged 65–95 years) 18.14 ± 7.33 pg/ml than those in the middle-aged group (aged 45–64 years) 14.35 ± 6.49 pg/ml when controlled gender and ApoEε4 carrier status (F = 3.102, P = 0.029). The ApoEε4 carriers had higher plasma tau levels than the non-carriers when controlled age and gender (F = 6.149, P = 0.001). Men had higher plasma tau levels than their women counterparts when controlled ApoEε4 carrier status and gender (F = 6.149, P = 0.001). The plasma tau levels were found to be positively associated with their ages (r = 0.359, P < 0.001). Regression analysis showed that age explained approximately 13% of the variance in the plasma tau levels, and explained more than 10% of the variance in the volumes of the hippocampus and white matter hypodensity (R2 change 0.123~0.167, all P < 0.001), and explained less than 10% of the variance in the volume of the amygdala, and central part of the corpus callosum (R2 change 0.085~0.097, all P = 0.001). However, the plasma tau levels do not further explain any residual variance in the volume of brain structures. In conclusion, the effect of age on the plasma tau levels should always be considered in clinical applications of this surrogate biomarker to middle-aged and elderly subjects.

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Section: Methodsmentioning

confidence: 97%

Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults

Chiu

Fan

Chen

et al. 2017

Front. Aging Neurosci.

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“…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%

“…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. The Aβ-42 to Aβ-40 concentration ratio and the tau levels in the blood are promising parameters or surrogate biomarkers for evaluating the risk of AD in the general population (Chiu et al, 2012, 2014). In this study, ultra-sensitive IMR was used to assay the plasma Aβ-40, Aβ-42 and tau levels in DS patients.…”

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.

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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.

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“…Among these technologies, the immunomagnetic reduction (IMR) technology stands out in its ability to measure three important AD pathology-associated proteins (Aβ 40 , Aβ 42 , and tau) [46]. Due to the unique principles on which this technology is based, IMR assays show ultrasensitivity in the detection of low amounts of the proteins in the non-blood-cell fraction of blood samples, plasma, collected from subjects diagnosed with preclinical AD and clinical AD dementia [47–50]. In a pilot study, the main objective was to assess the Aβ 40 , Aβ 42 , and tau levels measured by the ultrasensitive IMR assays in plasma samples.…”

Section: A New Tiered Approach To Diagnosing Alzheimer’s Diseasementioning

confidence: 99%

Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data

et al. 2017

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Establishing the in vivo diagnosis of Alzheimer’s disease (AD) or other dementias relies on clinical criteria; however, the accuracy of these criteria can be limited. The diagnostic accuracy is 77% for a clinical diagnosis of AD, even among experts. We performed a review through PubMed of articles related to specific diagnostic modalities, including APOE genotyping, cerebrospinal fluid (CSF) testing, fludeoxyglucose F 18 positron emission tomography (PET), amyloid PET, tau PET, computed tomography (CT), single-photon emission CT, magnetic resonance imaging (MRI), and B12 and thyroid-stimulating hormone screening, to determine the specificity and sensitivity of each test used in the clinical diagnosis of AD. We added a novel immunomagnetic reduction assay that provides ultrasensitivity for analyzing the levels of plasma tau and beta amyloid 42 (Aβ42). The sensitivity and specificity of the current diagnostic approach (structural CT or MRI with screening labs) remain low for clinical detection of AD and are primarily used to exclude other conditions. Because of limited diagnostic capabilities, physicians do not feel comfortable or skilled in rendering a clinical diagnosis of AD. Compounding this problem is the fact that inexpensive, minimally invasive diagnostic tests do not yet exist. Biomarkers (obtained through CSF testing or PET imaging), which are not routinely incorporated in clinical practice, correlate well with pathologic changes. While PET is particularly costly and difficult to assess, CSF measures of tau and beta amyloid are not costly, and these tests may be worthwhile when the tiered approach proposed here warrants further testing. There is a need for developing bloodborne biomarkers that can aid in the clinical diagnosis of AD. Here we present a streamlined questionnaire-enriched, biomarker-enriched approach that is more cost-effective than the current diagnosis of exclusion and is designed to increase clinical confidence for a diagnosis of dementia due to AD.

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New Assay for Old Markers-Plasma Beta Amyloid of Mild Cognitive Impairment and Alzheimer's Disease

Cited by 68 publications

References 0 publications

Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults

Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults

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

Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data

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