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Article
Clinical Meaningfulness in Alzheimer’s Disease Clinical Trials. A Report from the EU-US CTAD Task Force
Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer’s disease, following several decades of failure...
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Article
Open AccessThe 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...
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Open AccessCerebrospinal 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...
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Open AccessEvaluation 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...
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Open AccessSynaptic 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...
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Open AccessClinical 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...
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Open AccessDifferential 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...
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Article
Open AccessBioinformatics 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...
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Open AccessPublisher Correction: Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease
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Open AccessPlasma 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...
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Article
Open AccessP-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...
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Article
Open AccessDiagnostic 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...
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Open AccessClinical 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...
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Open AccessPlasma 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...
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Article
Open Accessβ-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...
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Article
Open AccessCSF 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...
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Article
Open AccessCritical 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...
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Article
Open AccessThe 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...
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Article
Open AccessNeurogranin 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...
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Article
Open AccessTDP-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...