Hugo Marcel Vanderstichele

Biomarkable bvba

Osteoporosis and Alzheimer’s disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amy...

Contexte Neuregulin1 (Nrg1) est un substrat présynaptique de la bêta-sécrétase 1 (BACE1) qui peut notamment activer les récepteurs ErbB4 post-synaptiques. Le gène Nrg1 a été associé à la schizophrénie. L’activation de la voie Nrg1/ErbB4 peut induire la synaptogenèse et la plasticité, améliorer l’expression des récepteurs NMDA et GABA et est neuropr...

Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare their performance with two commercial assays. Linearity, int...

Objectives: Cerebrospinal fluid α-synuclein (CSF α-syn) represents a possible biomarker in Parkinson's disease (PD) diagnosis. CSF blood contamination can introduce a bias in α-syn measurement. To date, CSF samples with a red blood cells (RBC) count >50 RBC × 106/L or haemoglobin (Hb) concentration >200 μg/L are excluded from biomarker studies. Ho...

Background CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (...

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-car...

The core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers amyloid beta (Aβ42 and Aβ40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between‐center differences in pre‐analytical procedures may contribute t...

Objective To study the genetic contribution to the start of Alzheimer's disease with amyloid and tau biomarkers in cognitively intact older identical twins. Methods We studied in 96 monozygotic twin‐pairs relationships between Aβ aggregation as measured by the ratio Aβ1‐42/1‐40 in cerebrospinal fluid (CSF, n=126) and positron emission tomography (...

Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma...

Abstract Background Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. Methods In this prospective cross-sectional study, we quantified plasma Aβ1–42/Aβ1–40 ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided...

Background: α-Synuclein is a small soluble protein, whose physiological function in the healthy brain is poorly understood. Intracellular inclusions of α-synuclein, referred to as Lewy bodies (LBs), are pathological hallmarks of α-synucleinopathies, such as Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Main body: Understanding of...

Background Formation of amyloid plaques and fibrillary tau tangles in brain are key pathological hallmarks in Alzheimer’s disease (AD). Surrogate biomarkers of these hallmarks have been established in CSF. However, a less invasive sample source would simplify the recruitment and the follow‐up of response in clinical trials targeting the pathologica...

Background The presynaptic protein Neuregulin1 (Nrg1) is cleaved by BACE 1 like amyloid precursor protein (APP), can activate post‐synaptic ErbB4 receptors and has been linked to schizophrenia. The couple Nrg1/ErbB4 is neuroprotective, can trigger synaptogenesis and plasticity and increases the expression of NMDA and GABA receptors. In addition thi...

Background Precise analysis of early changes in concentrations of proteins in cerebrospinal fluid (CSF) with qualified immunoassays can reflect the initiation or existence of Alzheimer’s Disease (AD) pathology in brains of affected subjects. Although CSF biomarkers are well established nowadays for use in clinical routine worldwide (eg. NIA AA guid...

Abstract Background Blood-based biomarkers for Alzheimer’s disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential of plasma markers Abeta(1-42/1-40), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) to iden...

Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinson's disease (PD) and other synucleinopathies. Therefore, the development of tools and methods to detect and quantify α-syn oligomer...

BACKGROUND Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms are essential to monitor treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare their performance with two commercial assays. METH...

Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42 ). They are intended to be used to calibrate diagnostic assays for Aβ42 . Methods: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three...

Background: 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 kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and pl...

Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinson's disease (PD) and other synucleinopathies. Therefore, the development of tools and methods to detect and quantify α-syn oligomer...

Objective: To study the genetic contribution to the start of Alzheimer's disease as signified by abnormalities in amyloid and tau biomarkers in cognitively intact older identical twins. Methods: We studied in 96 monozygotic twin-pairs relationships between Aβ aggregation as measured by the ratio Aβ1-42/1-40 in cerebrospinal fluid (CSF) and positron...

Abstract Background Dementia with Lewy bodies (DLB) is more prevalent in men than in women. In addition, post-mortem studies found sex differences in underlying pathology. It remains unclear whether these differences are also present antemortem in in vivo biomarkers, and whether sex differences translate to variability in clinical manifestation. Th...

Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's d...

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)assays for blood proteins, without providing reflections on a potential hypothesis of the origin of protein mismetabolism and deposition. There i...

Background: Aberrant amyloid-β (Aβ) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain Aβ load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aβ...

High levels of total α-synuclein (t-α-synuclein) in the cerebrospinal fluid (CSF) were reported in sporadic Creutzfeldt–Jakob disease (sCJD). The potential use of t-α-synuclein in the discrimination of Lewy body dementias (i.e., Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB)) is still under investigation. In addition, phosph...

The main pathophysiological alterations of Alzheimer's disease (AD) include loss of neuronal and synaptic integrity, amyloidogenic processing and neuroinflammation. Similar alterations can, however, also be observed in cognitively intact older subjects and may prelude the clinical manifestation of AD. The objectives of this prospective cross‐sectio...

Introduction: Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods: In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Result...

A Simoa research assay is developed to quantity Aβ1-42/Aβ1-40 in EDTA plasma samples. Feasibility data revealed good distinction between subjects with AD and healthy controls (selected based on CSF biomarker profiles) when using the ratio Aβ1-42/Aβ1-40. Results of the feasibility study were confirmed after transfer of the assay and initiation of th...

Background and Purpose— Inflammation is involved in the pathogenesis of large artery atherosclerosis, ischemic stroke, and Alzheimer dementia. However, the role of inflammation in cerebral small vessel disease and neurodegeneration remains poorly understood. We hypothesize that CRP (C-reactive protein) is associated with brain structural changes an...

α‐Synuclein is the major component of Lewy bodies (LBs) and a candidate biomarker for neurodegenerative diseases in which LBs are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterised by reduced concentrations of α‐synuclein in cerebrospinal fluid (CSF), with...

A novel ELISA for the quantification of tau phosphorylated at threonine 181 in cerebrospinal

Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ1-38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of...

Background: The core Alzheimer's disease cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), β-amyloid 1-42 (Aβ42) and β-amyloid 1-40 (Aβ40) are increasing in importance and are now part of the research criteria for the diagnosis of the disease. The main aim of this study is to evaluate whether a set of certified re...

Introduction: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. Methods: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We e...

Background: Cerebrospinal fluid (CSF) biomarkers (Aβ peptides and tau proteins) improved the diagnosis of Alzheimer’s disease (AD) in research and clinical settings. We previously described the PLM-scale (Paris-Lille-Montpellier study), which combines Aβ42, tau, and phosphorylated ptau(181) biomarkers in an easy to use and clinically relevant way....

Background and purpose: Cerebral small vessel disease (SVD) is a frequent pathology in aging and contributor to the development of dementia. Plasma Aβ (amyloid β) levels may be useful as early biomarker, but the role of plasma Aβ in SVD remains to be elucidated. We investigated the association of plasma Aβ levels with severity and progression of S...

The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access...

Background: To enhance the accuracy of clinical diagnosis for Alzheimer's disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in...

Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ1-38 relate to vascula...

Background: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression. Objective: To examine the association bet...

Background: Impaired olfactory function is an early characteristic of Alzheimer's disease (AD), but it remains unclear if odor identification also relates to early markers of AD in cerebrospinal fluid (CSF). Objective: To investigate the association between odor identification and amyloid-β 1-42 (Aβ42) and total tau (t-tau) concentrations in CSF...

Background: Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB) share clinical and molecular features. Cerebrospinal fluid (CSF) biomarkers may help the characterization of these diseases, improving the differential diagnosis. We evaluated the diagnostic perform...

Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson'...

With an increasing number of people with dementia worldwide, the measurement of biomarkers in cerebrospinal fluid (CSF) will be increasingly used as a routine diagnostic tool for diagnosis of Alzheimer’s disease (AD). The integration of a novel Phosphotau (pT181) ELISA in routine lab Environments requires assays with good analytical performance, ro...