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Clinical Meaningfulness in Alzheimer’s Disease Clinical Trials. A Report from the EU-US CTAD Task Force

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  1. Article

    Open Access

    The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

    Lack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synap...

    Shreyasee Das, Marie-Paule E. van Engelen, Julie Goossens in Alzheimer's Research & Therapy (2024)

  2. Article

    Open Access

    Cerebrospinal fluid proteomics in patients with Alzheimer’s disease reveals five molecular subtypes with distinct genetic risk profiles

    Alzheimer’s disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in...

    Betty M. Tijms, Ellen M. Vromen, Olav Mjaavatten, Henne Holstege in Nature Aging (2024)

  3. Article

    Open Access

    Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum

    Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer’s disease (AD). Vesicle-associated membran...

    Julie Goossens, Alba Cervantes González, Nele Dewit in Alzheimer's Research & Therapy (2023)

  4. Article

    Open Access

    Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer’s disease and frontotemporal dementia

    Loss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disea...

    Shreyasee Das, Julie Goossens, Dirk Jacobs, Nele Dewit in Alzheimer's Research & Therapy (2023)

  5. Article

    Open Access

    Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts

    Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer’s disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully refle...

    Juan Lantero-Rodriguez, Agathe Vrillon in Alzheimer's Research & Therapy (2023)

  6. Article

    Open Access

    Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring

    Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD patho...

    Nicholas J. Ashton, Shorena Janelidze, Niklas Mattsson-Carlgren in Nature Medicine (2022)

  7. Article

    Open Access

    Bioinformatics tools and data resources for assay development of fluid protein biomarkers

    Fluid protein biomarkers are important tools in clinical research and health care to support diagnosis and to monitor patients. Especially within the field of dementia, novel biomarkers could address the curre...

    Katharina Waury, Eline A. J. Willemse, Eugeen Vanmechelen in Biomarker Research (2022)

  8. Article

    Open Access

    Publisher Correction: Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

    Marta Milà-Alomà, Nicholas J. Ashton, Mahnaz Shekari, Gemma Salvadó in Nature Medicine (2022)

  9. Article

    Open Access

    Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

    Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer’s disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous bio...

    Marta Milà-Alomà, Nicholas J. Ashton, Mahnaz Shekari, Gemma Salvadó in Nature Medicine (2022)

  10. Article

    Open Access

    P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles

    We previously identified four Alzheimer’s disease (AD) subgroups with increasingly higher cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 181 (p-tau). These subgroups included individuals a...

    Kirsten E. J. Wesenhagen, Betty M. Tijms, Lynn Boonkamp in Alzheimer's Research & Therapy (2022)

  11. Article

    Open Access

    Diagnostic value of serum versus plasma phospho-tau for Alzheimer’s disease

    Blood phosphorylated tau (p-tau) forms are promising Alzheimer’s disease (AD) biomarkers, but validation in matrices other than ethylenediaminetetraacetic acid (EDTA) plasma is limited. Firstly, we assessed th...

    Przemysław R. Kac, Fernando Gonzalez-Ortiz, Joel Simrén in Alzheimer's Research & Therapy (2022)

  12. Article

    Open Access

    Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

    Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer’s disease (AD). We aimed to compare six P-tau Simoa assays, includ...

    Sherif Bayoumy, Inge M. W. Verberk, Ben den Dulk in Alzheimer's Research & Therapy (2021)

  13. Article

    Open Access

    Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology

    The quantification of phosphorylated tau in biofluids, either cerebrospinal fluid (CSF) or plasma, has shown great promise in detecting Alzheimer’s disease (AD) pathophysiology. Tau phosphorylated at threonine...

    Nicholas J. Ashton, Tharick A. Pascoal, Thomas K. Karikari in Acta Neuropathologica (2021)

  14. Article

    Open Access

    β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

    β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibit...

    Harald Hampel, Simone Lista, Eugeen Vanmechelen in Alzheimer's Research & Therapy (2020)

  15. Article

    Open Access

    CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

    The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein ki...

    François Mouton-Liger, Julien Dumurgier, Emmanuel Cognat in Alzheimer's Research & Therapy (2020)

  16. Article

    Open Access

    Critical Steps to be Taken into Consideration Before Quantification of β-Amyloid and Tau Isoforms in Blood can be Implemented in a Clinical Environment

    This review aims to document difficulties, limitations, and pitfalls when considering protein analysis in blood samples. It proposes an improved workflow for design, development, and validation of (immuno)assa...

    Hugo Marcel Vanderstichele, Charlotte E. Teunissen in Neurology and Therapy (2019)

  17. Article

    Open Access

    The elusive tau molecular structures: can we translate the recent breakthroughs into new targets for intervention?

    Insights into tau molecular structures have advanced significantly in recent years. This field has been the subject of recent breakthroughs, including the first cryo-electron microscopy structures of tau filam...

    Yann Fichou, Youssra K. Al-Hilaly, François Devred in Acta Neuropathologica Communications (2019)

  18. Article

    Open Access

    Neurogranin and tau in cerebrospinal fluid and plasma of patients with acute ischemic stroke

    While neurogranin has no value as plasma biomarker for Alzheimer’s disease, it may be a potential blood biomarker for traumatic brain injury. This evokes the question whether there are changes in neurogranin l...

    Ann De Vos, Maria Bjerke, Raf Brouns, Naomi De Roeck, Dirk Jacobs in BMC Neurology (2017)

  19. Article

    Open Access

    TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies

    Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia after Alzheimer’s disease. A high-ranking candidate to become a diagnostic marker for a major pathological subtype of FTLD is t...

    Joery Goossens, Eugeen Vanmechelen in Acta Neuropathologica Communications (2015)

  20. Article

    Potential sources of interference on Abeta immunoassays in biological samples

    Therapeutic products that depend on the use of an in vitro diagnostic biomarker test to confirm their effectiveness are increasingly being developed. Use of biomarkers is particularly meaningful in the context of...

    Hugo Vanderstichele, Erik Stoops, Eugeen Vanmechelen in Alzheimer's Research & Therapy (2012)

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