The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM).

Analyzer-to-Analyzer Variations in Assaying Ultralow Concentrated Biomarkers Associated with Neurodegenerative Diseases Using Immunomagnetic Reduction.

By utilizing a high-temperature superconducting quantum interference device (high- SQUID) magnetometer, an alternating current (AC) magnetosusceptometer, referred to as an analyzer, was developed for ultrasensitive immunoassays. The analyzer has been applied to assay biomarkers in human plasma associated with Alzheimer's disease (AD) and Parkinson's disease (PD). The involved assay methodology is the so-called immunomagnetic reduction (IMR).

Plasma Neurofilament Light Chains as Blood-Based Biomarkers for Early Diagnosis of Canine Cognitive Dysfunction Syndrome.

The number of elderly dogs is increasing significantly worldwide, and many elderly dogs develop canine cognitive dysfunction syndrome (CCDS). CCDS is the canine analog of Alzheimer's disease (AD) in humans. It is very important to develop techniques for detecting CDDS in dogs.

Development of a 36-Channel Instrument for Assaying Biomarkers of Ultralow Concentrations Utilizing Immunomagnetic Reduction.

With the demands of the high-throughput assay of biomarkers of ultralow concentrations in clinics, a 36-channel instrument utilizing immunomagnetic reduction (IMR) has been developed. The instrument involves the use of a high- superconducting-quantum-interference-device (SQUID) magnetometer to detect the signals due to the associations between target biomarker molecules and the antibody-functionalized magnetic nanoparticles in the reagent of IMR. In addition to illustrating the design and the measurements of the instrument, the assay characterizations for eight kinds of biomarkers related to neurodegenerative disease are investigated.

Applications of Immunomagnetic Reduction Technology as a Biosensor in Therapeutic Evaluation of Chinese Herbal Medicine in Tauopathy Alleviation of an AD Model.

Alzheimer's disease (AD) is the most common form of dementia. The most convincing biomarkers in the blood for AD are currently β-amyloid (Aβ) and Tau protein because amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with AD. The development of assay technologies in diagnosing early-stage AD is very important.

Relevance of plasma biomarkers to pathologies in Alzheimer's disease, Parkinson's disease and frontotemporal dementia.

Amyloid plaques and tau tangles are pathological hallmarks of Alzheimer's disease (AD). Parkinson's disease (PD) results from the accumulation of α-synuclein. TAR DNA-binding protein (TDP-43) and total tau protein (T-Tau) play roles in FTD pathology.

Effect of Time to Detection on the Measured Concentrations of Blood Proteins Associated with Alzheimer's Disease.

Background: For assays using immunomagnetic reduction, a reagent composed of antibody-functionalized magnetic nanoparticles is dispersed in phosphate-buffered saline solution. The real-time signals of alternating-current (ac) magnetic susceptibility, χ, of the reagent are subsequently recorded after mixing the reagent with a biofluid sample. After mixing the reagent and sample, the reduction in χ of the mixture is calculated and used to quantify the concentration of the target biomarker in the sample.

Synuclein Motor Dysfunction Composite Scale for the Discrimination of Dementia With Lewy Bodies From Alzheimer's Disease.

Background: An abnormal increase of α-synuclein in the brain is the hallmark of dementia with Lewy bodies (DLB). However, the diagnostic power of plasma α-synuclein in DLB is not yet confirmed. Parkinsonism is highly associated with and is one of the core clinical features of DLB.

Neurotherapy of Yi-Gan-San, a Traditional Herbal Medicine, in an Alzheimer's Disease Model of by Alleviating Aβ Expression.

Alzheimer's disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to the abnormal accumulation of amyloid β (Aβ) proteins. Yi-Gan-San (YGS), a traditional herbal medicine, has been used for the management of neurodegenerative disorders and for the treatment of neurosis, insomnia and dementia. The aim of this study was to examine antioxidant capacity and cytotoxicity of YGS treatment by using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in vitro.

Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aβ and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65).

Neurodegeneration and Vascular Burden on Cognition After Midlife: A Plasma and Neuroimaging Biomarker Study.

: Neurodegeneration and vascular burden are the two most common causes of post-stroke cognitive impairment. However, the interrelationship between the plasma beta-amyloid (Aβ) and tau protein, cortical atrophy and brain amyloid accumulation on PET imaging in stroke patients is undetermined. We aimed to explore: (1) the relationships of cortical thickness and amyloid burden on PET with plasma Aβ40, Aβ42, tau protein and their composite scores in stroke patients; and (2) the associations of post-stroke cognitive presentations with these plasma and neuroimaging biomarkers.

Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study.

Background: In Alzheimer's disease (AD), cognitive impairment begins 10-15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-β 1-42×total tau protein higher than 455 pg/ml are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD).

Assessing Plasma Levels of α-Synuclein and Neurofilament Light Chain by Different Blood Preparation Methods.

The potential biomarkers of Parkinson's disease are α-synuclein and neurofilament light chain (NFL). However, inconsistent preanalytical preparation of plasma could lead to variations in levels of these biomarkers. Different types of potassium salts of EDTA and different centrifugation temperatures during plasma preparation may affect the results of α-synuclein and NFL measurements.

The global Alzheimer's Association round robin study on plasma amyloid β methods.

Introduction: Blood-based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure Aβ and how they compare among centers and assays.

Methods: Aliquots from 81 plasma samples were distributed to 10 participating centers.

Investigation of the Number of Tests Required for Assaying Plasma Biomarkers Associated with Alzheimer's Disease Using Immunomagnetic Reduction.

Introduction: Concentrations of plasma biomarkers associated with Alzheimer's disease have been reported to be as low as several tens of picograms/milliliter (pg/ml). However, in assays measuring these biomarkers, it is likely that repeated measurements are necessary to obtain reliable values.

Methods: We performed assays as a single test or as duplicate, quadruplicate, fivefold and tenfold repeated tests, on samples spiked with different concentrations of amyloid β 1-40 (Aβ; 1-1000 pg/ml), Aβ (1-30,000 pg/ml) and total Tau protein (T-Tau; 0.

Synergistic Association between Plasma Aβ and p-tau in Alzheimer's Disease but Not in Parkinson's Disease or Frontotemporal Dementia.

Beta-amyloid (Aβ) triggers the phosphorylation of tau protein in Alzheimer's disease (AD), but the relationship between phosphorylated tau (p-tau) and Aβ in the blood is not elucidated. We investigated the association in individuals with AD ( = 62, including amnesic mild cognitive impairment and dementia), Parkinson's disease ( = 30), frontotemporal dementia ( = 25), and cognitively unimpaired controls ( = 41) using immunomagnetic reduction assays to measure plasma Aβ and p-tau181 concentrations. Correlation and regression analyses were performed to examine the relation between plasma levels, demographic factors, and clinical severity.

Plasma Total α-Synuclein and Neurofilament Light Chain: Clinical Validation for Discriminating Parkinson's Disease from Normal Control.

Background: A previously published paper (referred to as the original cohort) showed that using a cutoff value of 116.1 fg/mL for the plasma total α-synuclein concentrations could discriminate Parkinson's disease (PD) patients from normal controls (NCs). In this study, another independent cohort (referred to as the validation cohort) was recruited to validate the agreement between the clinical diagnosis and the use of plasma total α-synuclein to identify PD patients.

Immunomagnetic Reduction Detects Plasma Aβ Levels as a Potential Dominant Indicator Predicting Cognitive Decline.

Although the concentrations of Alzheimer's disease (AD) biomarkers Aβ, Aβ and tau protein are very low in human plasma, ultrasensitive assays such as immunomagnetic reduction (IMR) are able to precisely quantify them. Review articles have described the detailed working mechanism of IMR and revealed the feasibility of detecting early-stage AD by assaying these plasma biomarkers with IMR. In this review, we aimed to compare the significance of these plasma biomarkers in predicting cognitive decline in patients with Down syndrome, stroke, or amnestic mild cognitive impairment based on findings in the literature.

Effect of Times to Blood Processing on the Stability of Blood Proteins Associated with Dementia.

Background: The stability of proteins in the collecting tubes after blood draw is critical to the measured concentrations of the proteins. Although the guidelines issued by the Clinical and Laboratory Standards Institute (CLSI) suggest centrifugation should take place within 2 h of drawing blood, it is very difficult to follow these guidelines in hospitals or clinics. It is necessary to study the effect of times to blood processing on the stability of the proteins of interest.

Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.

Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit.

Plasma Levels of α-Synuclein, Aβ-40 and T-tau as Biomarkers to Predict Cognitive Impairment in Parkinson's Disease.

Objective: In this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson's disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR).

Methods: The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating.

Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.

Introduction: Pyroglutamate-modified amyloid β (Aβ) could be a biomarker for Aβ plaque pathology in the brain. An ultra-high-sensitive assay is needed for detecting Aβ.

Methods: Immunomagnetic reduction was used for quantification of Aβ in plasma from 46 participants.

Stability of Plasma Amyloid-β 1-40, Amyloid-β 1-42, and Total Tau Protein over Repeated Freeze/Thaw Cycles.

Introduction: Blood biomarkers of Alzheimer's disease (AD) have attracted much attention of researchers in recent years. In clinical studies, repeated freeze/thaw cycles often occur and may influence the stability of biomarkers. This study aims to investigate the stability of amyloid-β 1-40 (Aβ), amyloid-β 1-42 (Aβ), and total tau protein (T-tau) in plasma over freeze/thaw cycles.

Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease - A cross-validation study.

Blood-based biomarker assays of plasma β-amyloid (Aβ) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines.

Plasma and Serum Alpha-Synuclein as a Biomarker of Diagnosis in Patients With Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD. We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity.