An Introduction to Ultrasensitive Assays for Plasma Tau Detection

2021 ◽  
Vol 80 (4) ◽  
pp. 1353-1362
Author(s):  
Xu-Long Ding ◽  
Qing-zhang Tuo ◽  
Peng Lei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fiber Optics ◽  
Single Molecule ◽  
Biomarker Discovery ◽  
Diagnostic Value ◽  
Meso Scale Discovery ◽  
Reduction Assay ◽  
Low Sensitivity ◽  
Serologic Assay

The detection of plasma tau and its phosphorylation is technically challenging due to the relatively low sensitivity. However, in Alzheimer’s disease and other tauopathies, it is hypothesized that tau in the biofluid may serve as a biomarker. In recent years, several ultrasensitive assays have been developed, which can successfully detect tau and its phosphorylation in various biofluids, and collectively demonstrated the prognostic and diagnostic value of plasma tau/phosphorylated tau. Here we have summarized the principle of four ultrasensitive assays newly developed suitable for plasma tau detection, namely single-molecule array, immunomagnetic reduction assay, enhanced immunoassay using multi-arrayed fiber optics, and meso scale discovery assay, with their advantages and applications. We have also compared these assays with traditional enzyme-linked-immunosorbent serologic assay, hoping to facilitate future tau-based biomarker discovery for Alzheimer’s disease and other neurodegenerative diseases.

scholarly journals Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: a focused review on recent advances

2021 ◽  
pp. jnnp-2021-327370
Author(s):  
Joyce R. Chong ◽  
Nicholas J. Ashton ◽  
Thomas K. Karikari ◽  
Tomotaka Tanaka ◽  
Michael Schöll ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Emerging Technologies ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Phosphorylated Tau ◽  
Meso Scale Discovery ◽  
Aβ Peptides

Discovery and development of clinically useful biomarkers for Alzheimer’s disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring Aβ and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.

Differentiating Vascular Dementia from Alzhemer’s Disease with Brief Cognitive Tests

2014 ◽  
Vol 68 (1) ◽  
pp. 48-51
Author(s):  
Ivan Barbov ◽  
Ana Georgievska ◽  
Slavica Arsova ◽  
Snezhana Lazarova ◽  
Igor Petrov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Roc Curves ◽  
The Elderly ◽  
Diagnostic Value ◽  
Cognitive Tests ◽  
Delayed Recall ◽  
Common Causes ◽  
Low Sensitivity

Abstract Introduction. Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common causes of dementia in the elderly. The aim of this study was to investigate the diagnostic value of brief cognitive tests investigate the diagnostic value of brief cognitive tests in differentiating vascular dementia from Alzheimer’s disease. Methods. Fifteen patients with mild VaD, 15 patients with probable AD and 30 healthy controls, matched for age, education and dementia severity, were submitted to the following cognitive tests: clock drawing (free drqawing and copy), category of letter fluency, delayed recall test of figures and the EXIT 25 battery. Results. VaD patients performed worse than AD patients in category fluency (p=0.014), letter fluency (p=0.043) and CLOX 2 (p=0.023), while AD cases performed worse than VaD patients in delayed recall (p=0.013). However, Receiver Operating Characteristic (ROC) curves for these tests displayed low sensitivity and specificity for the differential diagnosis between VaD and AD. Conclusions. Altough the performance of VaD and AD patients was significantly different in some cognitive tests, the value of such instruments in differentiating VaD from AD proved to be very limited.

scholarly journals Limitations in differentiating vascular dementia from Alzheimer's disease with brief cognitive tests

2010 ◽  
Vol 68 (2) ◽  
pp. 185-188 ◽  
Author(s):  
Maria Niures P.S. Matioli ◽  
Paulo Caramelli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Recall Test ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Cognitive Tests ◽  
Delayed Recall ◽  
Clock Drawing ◽  
Low Sensitivity

OBJECTIVE: To investigate the diagnostic value of brief cognitive tests in differentiating vascular dementia (VaD) from Alzheimer's disease (AD). METHOD: Fifteen patients with mild VaD, 15 patients with mild probable AD and 30 healthy controls, matched for age, education and dementia severity, were submitted to the following cognitive tests: clock drawing (free drawing and copy), category and letter fluency, delayed recall test of figures and the EXIT 25 battery. RESULTS: VaD patients performed worse than AD patients in category fluency (p=0.014), letter fluency (p=0.043) and CLOX 2 (p=0.023), while AD cases performed worse than VaD patients in delayed recall (p=0.013). However, ROC curves for these tests displayed low sensitivity and specificity for the differential diagnosis between VaD and AD. CONCLUSION: Although the performance of VaD and AD patients was significantly different in some cognitive tests, the value of such instruments in differentiating VaD from AD proved to be very limited.

scholarly journals Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lanyu Zhang ◽  
Tiago C. Silva ◽  
Juan I. Young ◽  
Lissette Gomez ◽  
Michael A. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Prefrontal Cortex ◽  
Biomarker Discovery ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Braak Stage ◽  
Polycomb Repressive Complex 2 ◽  
Differentially Methylated Genes

AbstractDNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.

scholarly journals Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration

2020 ◽  
Vol 26 (3) ◽  
pp. 387-397 ◽  
Author(s):  
Elisabeth H. Thijssen ◽  
◽  
Renaud La Joie ◽  
Amy Wolf ◽  
Amelia Strom ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Diagnostic Value

scholarly journals Full-length and C-terminal neurogranin in Alzheimer’s disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Annika Öhrfelt ◽  
Julien Dumurgier ◽  
Henrik Zetterberg ◽  
Agathe Vrillon ◽  
Nicholas J. Ashton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Single Molecule ◽  
Full Length ◽  
The Novel ◽  
Drug Candidates ◽  
Postsynaptic Protein ◽  
Coefficients Of Variation ◽  
Assay Precision ◽  
Novel Drug

Abstract Background Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease. Methods In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26). Results The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785). Conclusions Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.

P1-171: Added Diagnostic Value of Cerebrospinal Fluid Neurogranin in the Classification of Prodromal and Alzheimer’s Disease Dementia

2016 ◽  
Vol 12 ◽  
pp. P468-P468
Author(s):  
Simone Lista ◽  
Nicola Toschi ◽  
Francesco Garaci ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Diagnostic Value ◽  
Alzheimer’S Disease Dementia
Sign in / Sign up

Export Citation Format

Share Document