Current state and future directions of neurochemical biomarkers for Alzheimer's disease

Jong, Daniëlle de; Kremer, Berry; Rikkert, Marcel G M Olde; Verbeek, Marcel M.

doi:10.1515/cclm.2007.320

Cited by 75 publications

(57 citation statements)

References 165 publications

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“…7,8 In Alzheimer disease, decreased concentrations of Ab 42 and elevated concentrations of total tau (t-tau) and phosphorylated tau (p-tau) have been detected in the CSF. 9 In patients with sCAA with advanced vascular damage, decreased CSF Ab 42 and Ab 40 and mildly elevated t-tau and p-tau concentrations have been found. 10,11 We aimed to find biomarkers of the earliest, potentially reversible phases of CAA.…”

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confidence: 97%

β-Amyloid in CSF

et al. 2017

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Objective: To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of b-amyloid (Ab).Methods: HCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers. CSF concentrations of Ab 40 , Ab 42 , total tau, and phosphorylated tau 181 proteins were compared to those of controls of a similar age. Correlations between CSF biomarkers, MRI markers, and age were investigated with multivariate linear regression analyses.Results: We included 10 symptomatic patients with HCHWA-D (mean age 55 6 6 years), 5 presymptomatic HCHWA-D carriers (mean age 36 6 13 years), 31 controls ,50 years old (mean age 31 6 7 years), and 50 controls $50 years old (mean age 61 6 8 years).

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confidence: 97%

β-Amyloid in CSF

et al. 2017

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“…One of the driving forces of proteomics in drug development is the discovery of biomarker candidates of potential clinical relevance in the periphery [14][15][16]. Due to its proximity to the brain and clinical availability, CSF is a unique medium by which to detect biochemical changes in the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Cerebrospinal Fluid by 8-Plex iTRAQ Reveals Potential Biomarker Candidates of Alzheimer’s Disease

Guerreiro

Gomez‐Mancilla

Williamson³

et al. 2009

Clin Proteom

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Introduction Alzheimer’s disease (AD) poses specific challenges for drug development. It has a slow and variable clinical course, an insidious onset, and symptom expression is only observed when a significant proportion of neurons are already lost. Discussion Determinants of clinical course, such as molecular biomarkers, are urgently needed for early detection and diagnosis, or for prognosis and monitoring disease-modifying therapies in stratified patient populations. Due to its proximity to the brain and clinical availability, cerebrospinal fluid (CSF) is likely to have the highest yield of biomarker potential for neurodegenerative diseases. In this study, we examined the feasibility of using of an 8-plex isobaric tagging approach, coupled to two-dimensional liquid chromatography and tandem mass spectrometry using the matrix-assisted laser desorption/ionization time-of-flight/time-of-flight platform, for the discovery of potential biomarker candidates in CSF. Comparative analysis identified a number of statistically significant differences in the level of proteins when comparing AD to nondemented controls. Although the study is statistically underpowered to represent the disease population, the regulation of proteins with involvement in processes such as neuronal loss, synaptic dysfunction, neuroinflammation, and tissue degeneration and remodeling reflects the ability of our method in providing biologically meaningful CSF biomarkers as candidates for larger scale biomarker verification and validation studies.

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“…1,2 To reach this goal, the measurement of extremely low concentrations of proteins in serum is necessary. [3][4][5][6][7] At the same time, point-of-care medical diagnostics represents one of today's main challenges towards the promise of tests that can be carried out at the site of patient care. 8 From the immunoassay integration perspective, this has been translated in terms of miniaturization of the detection systems and reduction of the sample and reagent volumes needed for the analysis.…”

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Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

et al. 2014

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ABSTRACT. We describe the concept of magnetic particle-scanning for on-chip detection of biomolecules: a magnetic particle, carrying a low number of antigens (Ags) (down to a single molecule), is transported by hydrodynamic forces and is subjected to successive stochastic reorientations in an engineered magnetic energy landscape. The latter consists of a pattern of substrate-bound small magnetic particles that are functionalized with antibodies (Abs). Subsequent counting of the captured antigen-carrying particles provides the detection signal. The magnetic particle-scanning principle is investigated in a custom-built magneto-microfluidic chip and theoretically described by a random walk-based model, in which the trajectory of the contact point between an antigen-carrying particle and the small magnetic particle pattern is described by

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Current state and future directions of neurochemical biomarkers for Alzheimer's disease

Cited by 75 publications

References 165 publications

β-Amyloid in CSF

β-Amyloid in CSF

Proteomic Profiling of Cerebrospinal Fluid by 8-Plex iTRAQ Reveals Potential Biomarker Candidates of Alzheimer’s Disease

Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

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