9 research outputs found
CSF biomarkers in Olmsted County: Evidence of 2 subclasses and associations with demographics
ObjectiveWe studied interrelationships between CSF biomarkers and associations with APOE ϵ4 genotype, demographic variables, vascular variables, and clinical diagnosis in Olmsted County, Minnesota.MethodsWe included 774 Mayo Clinic Study of Aging participants (693 cognitively unimpaired [CU]; 71 with mild cognitive impairment [MCI]). CSF β-amyloid 42 (Aβ42), total tau (t-tau), and hyperphosphorylated tau (p-tau) were analyzed using Aβ42 CSF, t-tau CSF, and p-tau (181P) CSF electrochemiluminescence immunoassays. Bivariate mixture models were used to evaluate latent classes. We used linear regression models to evaluate independent associations of APOE ϵ4, demographic factors, cardiovascular risk, and diagnosis with CSF biomarker levels. Results were weighted back to the Olmsted County population.ResultsInterrelationships between CSF Aβ42 and p-tau/t-tau were consistent with 2 latent classes in the general population. In subgroup 1 (n = 547 [71%]), we found a strong positive correlation between Aβ42 and p-tau (ρ = 0.81), while the correlation was much smaller in group 2 (ρ = 0.26, n = 227 [29%]). Group 2 was associated with older age, APOE ϵ4 genotype, a diagnosis of MCI, and elevated amyloid PET. Overall, APOE ϵ4 genotype and MCI were associated with Aβ42, while age was associated with p-tau/t-tau. There were no associations with sex, education, or vascular risk.ConclusionWe hypothesize the population without dementia can be subdivided into participants with and without biological Alzheimer disease (AD) based on the combination of CSF Aβ42 and p-tau/t-tau (represented also by the p-tau/t-tau/Aβ42 ratio). In those without biological AD, common factors such as CSF dynamics may cause a positive correlation between CSF Aβ42 and p-tau/t-tau, while AD leads to dissociation of these proteins
Cerebrospinal fluid biomarkers for Alzheimers disease : a view of the regulatory science qualification landscape from the coalition against major diseases CSF biomarker team
Abstract Alzheimer’s disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development
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Blood‐based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases
Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design
The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their result
Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design
Introduction The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI) Methods ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. Results Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. Discussion Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results
Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer’s disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility as well as an unclear path for moving basic discovery towards clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state-of-the-art. Additionally, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and towards clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional hand-off model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases