Diagnostic and Prognostic study (DPMS)
The AMYPAD DPMS will select and follow-up a memory clinic population suspected of possible AD, focusing on those with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and dementia where AD is in the differential diagnosis (900 subjects in 3 strata: SCD plus, MCI, dementia possibly due to AD), to determine the usefulness of β-amyloid imaging with regards to diagnostic confidence, decision trees, change in diagnosis, and alterations between planned and actual patient management plans. There are 8 active sites, 617 reserach participants and 408 scans performed (Last update January 2020). For more information please visit:
Prognostic and Natural History study (PNHS)
The AMYPAD PNHS will select and follow-up a natural history population ranging from cognitively normal, through subjective cognitive decline (SCD) towards mild cognitive impairment (MCI) due to early AD to better understand the natural history of the early disease phases and to evaluate the value of quantitative PET amyloid imaging measures for predicting progression within an Alzheimer's disease risk probability spectrum based on quantitative PET amyloid imaging measures, with or without other biomarkers through an intimate collaboration with EPAD and other non-EPAD cohorts. There are 9 active sites, 2 parent cohorts, 378 research participants and 297 scans performed (Last update January 2020). For more information, please visit:
EMIF-AD multimodal biomarker discovery study (MBD)
The EMIF-AD MBD study aimed to accelerate the discovery of novel diagnostic and prognostic biomarkers for AD and to unravel the underlying pathophysiological mechanisms using existing data and samples. The EMIF-AD MBD includes harmonized and pooled clinical data from 11 cohort studies across Europe and samples (cerebrospinal fluid, plasma, DNA) and MRI scans which were centrally analyzed using different omics techniques (proteomics, metabolomics, genomics). In total, material from 1221 participants was included (n=492 control, n=527 MCI, n=202 AD dementia). Data requests can be submitted via the EMIF-AD Catalogue. For more information, please visit:
EMIF-AD 90+ study
The EMIF-AD 90+ study aimed to identify factors associated with resilience to cognitive impairment in the oldest-old. The study was conducted at the Amsterdam University Medical Center and at the University of Manchester. At baseline, neuropsychological and clinical data (vascular comorbidities, mood, sleep, physical performance, genetic factors) were collected from 129 participants (n=84 with normal cognition and n=38 with cognitive deficits). Regarding imaging measures: baseline MRI (n=92), Amyloid-PET (n=103) and MEG (n=92) have been collected. In addition, skin biopsies (n=99) and ultrasound of the carotid artery (n=102) are also collected. Currently (Oct 2019), the first annual follow-up measurements have completed in n=129 as of November 2019, with plans for a second annual follow-up 2020. Data requests can be submitted via the EMIF-AD catalogue. For more information, please visit:
EMIF-AD PreclinAD study
The EMIF-AD PreclinAD study aimed to indentify new risk factors and diagnostic markers for both amyloid pathology and cognitive decline in cognitively normal subjects with or without amyloid pathology. To investigate this, monozygotic twin pairs were included such that genetic and environmental pathways can be identified. For the baseline measurement n=204 cognitively healthy elderly monozygotic twins aged 60 years and older were included from the Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twin Register. At baseline the following measurements were done: neuropsychological examination (n=204), blood sampling (n=204), CSF collection (n=127), ultrasound of the carotid artery (n=102), magnetoencephalography (n=190) and collection of ophthalmological markers (n=198). In n=192 (94%) the following follow-up measures were done after two years: containing a neuropsychological examination (n=191), blood collection (n=192) and CSF sampling (n=103). A second follow-up will be conducted in 2020. Data requests can be submitted via the EMIF-AD catalogue. For more information, please visit:
Longitudinal Cohort Study (LCS)
The EPAD LCS is an ongoing prospective, multicentre, pan-European longitudinal cohort study. Participants are recruited mainly from existing parent cohorts across Europe to form a ‘probability-spectrum’ population covering the entire continuum of anticipated probability for Alzheimer’s dementia development. The primary objective of the EPAD LCS is to be a readiness cohort for the EPAD PoC trial though a second major objective is to generate a comprehensive and large data set for disease modelling of preclinical and prodromal Alzheimer’s disease. The number of research participants is 1991 (Last update January 2020). The LCS is led by University of Edinburgh. For more information, please visit:
AETIONOMY PD cohort
The AETIONOMY PD study was a multi-centre, cross-sectional clinical study that recruited participants from 6 sites across 3 European countries, aiming to validate the mechanism-based taxonomies generated by the AETIONOMY project. Total n=405 (clinical data), including n=25 with genetic PD, n=251 idiopathic PD, n=39 at risk of PD, n=90 healthy controls. MRI imaging is available for 30 participants, see 'Bio Samples' for list of biological samples and specimens available from the cohort. Data from a multi-omics approach were also collected. For more information, please see:
Cohort of patients with recurrent depressive disorder who will use RMT
This is a a multicentre observational cohort study (RADAR-MDD). Patients with recurrent depressive disorder using RMT will be included. Also, information regarding clinical outcomes (particularly, though not exclusively, recurrence and relapse) over the course of 12 months will be added. For more information please visit:
Cohort of MS patients
This is a prospective multicenter cohort study conducted in all three MS centres involving MS patients with relapsing remitting and progressive disease and with an EDSS between 2.0 and 6.0 (i.e. fully ambulatory patients with mild disability to patient able to walk with a single aid for at least 100 m). For more information please visit:
Cohort of epilepsy patients with ongoing seizures despite treatment
This is multi-centre observational clinical cohort study (RADAR-EPILEPSY) of adult patients with either, or both, GTCS or FS, who have ongoing seizures despite treatment. The participants will undergo detailed baseline interviews. For more information please visit:
Disease relevant cohorts of hiPSC lines
EBiSC can provide cohorts of iPSC lines which are familially and/or isogenically related such as collections of lines derived from age and sex matched Alzheimer's Disease patients which have then been gene edited to carry all ApoE variants + knockout. For some diseases, a range of genotypes are also available which are designed to reflect population variances, for example, a range of Huntington's disease lines which carry variable HTT CAG repeat lengths. For more information, please visit:
Omics data from iPSC cells, humanised ApoE mouse models
ADAPTED has collected RNA from iPSC-generated neurons, microglia, patient-derived monocytes and humanised APOE mouse models, and will collect RNA from iPSC-generated astrocytes and macrophages. Methylome analysis has been completed for patient-derived monocytes. Proteomics analysis has been completed for iPSC-derived astrocytes, iPSC-derived macrophages, iPSC-derived microglia, humanised APOE mouse models. Metabolomics analysis has been completed for iPSC-derived neurons and astrocytes. Datasets will be available after the end of the project embargo period. For more information, please visit:
Animal data from multi-site experiments
EQIPD has obtained study reports for historical data from EFPIA partners, CROs and academic labs, and calculate the prevalence of reporting of measures to increase internal validity. An initial survey of available datasets suggests availability for the Irwin test (47 experiments), Morris Water Maze (69), Y/T mazes (50), prepulse inhibition (56), novel object recognition tasks (35), and sleep/wake (72) and circadian (37) EEG. For mroe information, please visit:
Omics data on patient tissue and cellular disease models
IM2PACT will identify genes or pathway candidates associated with neurodegenerative diseases and expressed in brain endothelial cells. To fulfil this aim IM2PACT will use genetic analyses of existing data (GWAS, others); transcriptomic, proteomic on patient primary cells or tissues; transcriptomic, proteomic on preclinical disease models primary cells and glycomics of BBB cells and/or cerebral vasculature of diseased brains. For more information please visit:
Genetic screens for tau and alpha-synuclein aggregation
IMPRiND has performed genetic screens to identify modifiers of alpha-synuclein and tau aggregation. These include both focused and genome-wide screens. Data will become available upon completion of the analysis and deposition to open access repositories. For more information please visit:
Publically available data on hiPSC lines and donors
Each hiPSC line has a core dataset which is publically available via the EBiSC catalogue. This includes donor age, biological sex, disease status and genotype (if relevant), reprogramming method, culture conditions and characterisation. Additionally, any restrictions for use and third party licensing obligations are also openly available via the Cell Line Information Pack. For more information, please visit:
Personal Data through DAC
Data defined as 'Personal Data' by GDPR such as short tandem repeat data and whole genome sequencing is available by application to the EBiSC Data Access Committee (see Platform). Apply for access via email@example.com
Omics data from CSF/plasma from MCI patients
ADAPTED has generated proteomics and metabolomics datasets from CSF and plasma samples from MCI patients. Datasets will be available after the end of the project embargo period. For more information, please visit:
Clinical, neuroimaging and -omics datasets from AETIONOMY PD study
The AETIONOMY PD study generated clinical, neuroimaging and -omics datasets from n=405 participants (clinical data), including n=25 with genetic PD, n=251 idiopathic PD, n=39 at risk of PD, n=90 healthy controls. MRI imaging is available for 30 participants. For more information, please see:
Neuroimaging datasets from the AMYPAD PNHS and DPMS studies
AMYPAD's PET and MRI imaging data set releases will be made available via collaborative workspaces. These data set releases will only include de-identified and cleaned data, from the Diagnostic and Patient Management Study (DPMS) and the Prognostic and Natural History Study (PNHS). Recruitment of the DPMS should be completed in 2020, with results expected in 2021. The data management activities have been started to ensure a clean dataset for the next step of data analysis. Recruitment of the PNHS is ongoing. The AMYPAD PNHS data will be made publicly available in the future. In line with the EPAD project, data locks will occur at least at V.1000, V.1500 and V.2000. Information on the PNHS data dictionary can be found here: https://amypad.eu/wp-content/uploads/2019/11/AMYPAD-PNHS-Parent-Cohort-Data-Dictionary-v0.1.pdf. For more information on the AMYPAD imaging datasets, please visit:
Clinical, neuroimaging and -omics datasets from EMIF-AD MBD, 90+ and PreClinAD studies
The EMIF-AD multimodal biomarker discovery study (MBD), 90+ study and PreClinAD studies generated clinical and neuropsychiatric datasets, imaging and -omics data (see "Cohort" asssets for more details of these clinical studies). The EMIF-AD datasets are available on TranSMART through the EMIF catalogue:
Clinical, biomarker and neuroimaging data from the EPAD LCS study
The EPAD LCS data is made available in secure online Workspaces in order to facilitate collaboration between people and teams with similar research aims. The dataset definition document can be accessible on the ERAP page of the EPAD website along with the different versions of the EPAD protocol, videos and tutorial to access the data. For more information, please visit:
Neuroimaging data from the KCL neuroimaging study
PHAGO will perform prospective human clinical Positron Emission Tomography (PET) scanning of neuroinflammation in a very small group (MMSE=20) with/ without TREM2 R47H alleles (at KCL). For more information please visit:
Real-world data from RADAR-AD study of multiple wearable and digital devices
RADAR-AD will undertake a prospective multi-center study to test different types of remote monitoring technology (RMT). RADAR-AD will test wearables, portable technologies and fixed sensors. Study numbers: n = 50 preclinical AD, n = 60 prodromal AD, n = 70 mild/moderate AD, n= 40 healthy controls. Data will be captured and modelled using the RADAR-BASE platform (https://radar-base.org/index.php/home/about-us/). For more information, please visit:
Biosamples from people with AD, MCI, or healthy individuals
Sample collections obtained from 1,193 individuals (blood, DNA, plasma, serum, saliva and CSF) have been generated by Fundació ACE and have been registered in the Spanish national registry of biobanks (Instituto de Salud Carlos III Reg. num. C.0000299). The repository is accessible for research purposes to anyone interested. Sample access requests are reviewed and negotiated individually, regulated by Spanish legislation (Royal Decree 1716/2011; Act 14/2007) . A Materials and Data transfer agreement (MDTA) is signed between Fundació ACE and research groups requesting access to this collection. For more information please visit:
DNA, CSF, plasma, serum and fibroblasts samples from the AETIONOMY PD study
The AETIONOMY PD study was a multi-centre, cross-sectional clinical study that recruited participants from 6 sites across 3 European countries, aiming to validate the mechanism-based taxonomies generated by the AETIONOMY project. The AETIONOMY PD study generated DNA (n=396), CSF (n=99), plasma (n=391), serum (n=391) and fibroblast samples (n=160) from the 405 participants recruited to the AETIONOMY PD cohort study. Sample sharing requests should be addressed to Jean-Christophe Corvol at the ICM in Paris. For more information, please see:
Plasma, DNA and CSF from participants of the EMIF-AD Multimodal biomarker discovery study (MBD)
The EMIF-AD MBD study aimed to accelerate the discovery of novel diagnostic and prognostic biomarker for AD and to unravel the underlying pathophysiological mechanisms using existing data and samples. In total, 1221 participants were recruited to the MBD study(n=492 control, n=527 MCI, n=202 AD dementia). Plasma from 1189 participants, DNA from 929 participants and CSF from 775 participants was obtained. For more information please visit:
Blood samples, CSF and skin biopsies from participants of the EMIF-AD 90+ study
The EMIF-AD 90+ study aimed to identify factors associated with resilience to cognitive impairment in the oldest-old, including 84 participants with normal cognition and 38 with cognitive deficits. The first annual follow-up measurements were completed in n=129 as of November 2019, with plans for a second annual follow-up 2020. Biological samples collected are as follows: 104 blood samples, 99 skin biopsies and 36 samples of CSF. For more information, please visit:
Blood and CSF from participants of the EMIF-AD PreclinAD study
The EMIF-AD PreclinAD study aimed to indentify new risk factors and diagnostic markers for both amyloid pathology and cognitive decline in cognitively normal subjects with or without amyloid pathology. To investigate this monozygotic twin pairs were included such that genetic and environmental pathways can be identified. At baseline the following samples were obtained: blood (n=204), CSF (n=127). In n=192 (94%) the following follow-up measures were done after two years: blood collection (n=192) and CSF sampling (n=103). A second follow-up will be conducted in 2020. For more information please visit:
Longitudinal Cohort Study biosamples
The EPAD LCS is an ongoing prospective, multicentre, pan-European longitudinal cohort study. Participants are recruited mainly from existing parent cohorts across Europe to form a ‘probability-spectrum’ population covering the entire continuum of anticipated probability for Alzheimer’s dementia development. The EPAD LCS study has collected CSF, blood, urine and saliva samples in its BioBank, currently located at the Roslin Research Institute at the University of Edinburgh. These samples will be used for future biomarker assessments (emerging AD biomarkers). For more information please see:
CSF samples from the TREM2 variant cohort of KCL
PHAGO will search for novel microglia related biomarkers in the CSF of AD patients using advanced mass spectrometry technologies for allowing a better monitoring of potential therapies. Samples will be obtained from participants in the TREM2 variant cohort (R47H) at KCL. For more information please visit:
EMIF-AD data Catalogue
The EMIF Platform is an IT platform that allows access to multiple, diverse data sources. The EMIF Catalogue, part of the EMIF platform, allows users to explore population-based and cohort-derived (predominately AD) data sources who have consented to provide such information for the purposes of bona fide researchers wanting to explore potential data partners for studies. The EMIF Platform makes this data available for browsing and allows exploitation in multiple ways by the end user. The EMIF Platform has leveraged data on more then 62 million European adults and children by means of federation of healthcare databases and cohorts from 7 different countries (DK, IT, NL, UK, ES, EE), designed to be representative of the different types of existing data sources (population-based registries, hospital-based databases, cohorts, national registries, biobanks, etc.). For more information, please visit:
Tools for federated EHR analysis
The EMIF-Platform has leveraged data on more then 62 Million European adults and children by means of federation of healthcare databases and cohorts from 7 different countries (DK, IT, NL, UK, ES, EE), designed to be representative of the different types of existing data sources (population-based registries, hospital-based databases, cohorts, national registries, biobanks, etc.). The data is represented in the EMIF Data Catalogue. For more information, please visit:
Trial Delivery Centre (TDC) network
The EPAD Trial Delivery Centre (TDC) network is formed by the TDCs contributing to the EPAD LCS study and intending to participate in the EPAD PoC study. EPAD currently has 28 study sites and plans to initiate 40 TDCs prior to the end of the IMI funding period (June 2020). The TDCs that are part of the TDC network have been certified and approved by the Chief Investigator (CI) & the Sponsor (UEDIN). For more information please visit:
The EPAD Register
The EPAD register is a pan-European register of over half a million people across the risk spectrum for dementia, led by VUMC and Pfizer. It has been developed to function as a reservoir of potential research participants for the EPAD LCS study. It is made up of a set of collaborating Parent Cohorts (PCs) across Europe that remain independent and secure, but simultaneously constitute a ‘virtual’ collection of subjects from which suitable participants can be discovered and selected, on the basis of known risk factors and markers, for the trial-ready LCS. The EPAD Register will also be the main source of recruitment to EPAD PoC from 2021. For more information please visit:
Proof of Concept Trial Platform
The EPAD PoC trial platform is available to any pharmaceutical company or biotech interested in testing a compound in PhII for the prevention of AD. It uses the TDC network, recruits from EPAD LCS and EPAD Register. The PoC Platform facilitates for different Intervention Owners to run their Appendix on the PoC trial, with the University of Edinburgh as the trial Sponsor and IQVIA as the Trial CRO. The PoC trial platform is based on a Master PoC Protocol and Intervention Owner-specific Appendices. The PoC trial allows an adaptive design including an equal randomisation across Appendices and a 3:1 randomisation within each Appendix to active treatment and placebo. Within the PoC trial, placebo arms can be shared across different Intervention Owners. Intervention Owners can approach EPAD by email firstname.lastname@example.org. For more information, please visit:
Radar Base Platform
An open source platform for integrating data streams from various wearable devices and mobile applications The comprehensive end-to-end platform will support research on RMT beyond the focus of this project. The platform will be: (a) flexible, allowing new devices/parameters to be added; (b) sustainable – such that the same underlying platform can be used to study different disease to those specified in the call; (c) patient friendly – such that monitoring is unobtrusive, protects privacy, and is engaging for patients by providing feedback; and (d) interconnected – integrating RMT data with conventional clinical outcome/EHR data. For more information please visit:
Data collected in cohort studies lay the groundwork for a plethora of Alzheimer’s disease (AD) research endeavors. ADataViewer lets you explore this AD data landscape and identify cohort datasets that suit your research needs.
We accessed and curated major AD cohort datasets in a purely data-driven manner with the aim of 1) characterizing their underlying data, 2) assessing the quantity and availability of data, and 3) evaluating the interoperability across these distinct cohort datasets. All displayed results are based on the data that were shared and made accessible to the curators.
The AETIONOMY NeuroMMSig server is a knowledge base representing essential pathophysiology mechanisms of neurodegenerative diseases. Together with dedicated algorithms, this knowledge base forms the basis for a “mechanism-enrichment server” that supports the mechanistic interpretation of multiscale, multimodal clinical data. For more information please visit:
EBiSC public catalogue
A public catalogue which displays hiPSC line related information such as donor sex, age at sampel collection, diagnosed condition(s), disease associated genotype (where relevant) and purchasing requirements. For more information, please visit: https://cells.ebisc.org/
EBiSC Data Access Committee
A data access committee (DAC) which acts on behalf of the data depositor to manage access to Personal Data such as STR profiles, whole genome sequencing and/or clinical phenotyping, amongst others. Researchers who hold Personal Data associated with EBiSC hiPSC lines can deposit their data into the European genome-phenome archive (EGA). External users then apply to the EBiSC DAC to gain access. EBiSC DAC performs due diligence to ensure they are a legitimate researcher and asks for agreement that data is only to be used for designated purpose and then grants access to the data on behalf of the data depositor. For more information, please visit:
The human pluripotent stem cell registry (hPSCreg) is a publicly available data portal/registry for pluripotent cell lines. EBiSC uses hPSCreg to collect infromation regarding the tissue donor, the hiPSC derivation process and cell line characterisation for all its lines. For more informatio, please visit:
Biomedical Knowledge Miner from Fraunhofer
The Biomedical Knowledge Miner (BiK>Mi) provides tools to access and validate knowledge encompassing all of the latest information pertaining to Alzheimer's Disease. This project aims to use a comprehensive computational model of biological mechanisms in the context of Alzheimer's Disease to determine currently used drugs that can effectively treat this disease. This drug repurposing workflow would significantly expedite development and research time as well as be applied to a variety of diseases.
iPSC-derived cell models of ApoE risk alleles
To model the cellular effects of ApoE genotypes in vitro, ADAPTED has used genome editing to generate iPSC lines with different ApoE genotypes (isogenic, E2, E3 or E4 alleles), which have been differentiated into various cell lineages (astrocytes, neurons, macrophages, microglia). For more information, please visit:
In silico model of neurodegenerative disease mechanisms
AETIONOMY has used information retrieval and data mining to generate hypotheses (candidate mechanisms for both diseases AD/PD) based on the AETIONOMY knowledge database. Analyses performed by scientific research partners confirmed the importance of several biological pathways in the pathogenesis of AD/PD also providing further details on the pathways and biomarkers involved. Together, the in silico modelling and in vitro confirmation studies generated 7 new disease mechanisms, which have been selected for validation using AETIONOMY clinical study samples. For more information, please visit:
HiPSC lines derived from >37 different disease backgrounds
EBiSC has safeguarded >900 hiPSC lines through research teams across Europe and USA depositing their hiPSC lines into EBiSC. Each line has a recorded history, has been characterised and qualified and is available to purchase by both non-profit and commercial organisations via our online catalogue. This includes hiPSC lines from a 'healthy' background, gene edited lines and lines derived from individuals with diagnosed diseases. HiPSC lines derived from individuals with diagnosed diseases including neurological, neurodegenerative, cardiac, eye, blood, kidney, liver, immunological and rare diseases. Information on the disease status and link to any familial controls is available via the catalogue. Where available, disease associated genotypes are recorded and also available. HiPSC lines from 'healthy backgrounds include hiPSC lines from different ethnicities which are age and sex matched. Tool lines which have been gene-edited to simplify differentiation are also available, for example, inducible NGN2 to drive rapid and stable neuronal differentiation. Genomic data such as whole genome sequencing and/or SNP arrays may also be available as managed access via application to the EBiSC Data Access Committee. For more information, please visit:
In vitro and in silico models of the blood-brain barrier
IM2PACT will develop state-of-the-art in vitro blood-brain barrier (BBB) models by differentiating hiPSC into brain endothelial cells; it will also use mathematical modelling of receptor/carrier-mediated transcytosis across the BBB and pharmacokinetics of biopharmaceutics in the brain to create in silico BBB models reproducing/predicting disease features and BBB permeability in vivo, in both healthy and disease states. For more information, please visit:
iPSC-based and organotypic cultures, neuronal models and animal models of alpha-synuclein or tau aggregation or propagation
IMPRiND has developed a number of models to investigate fibril-induced alpha-synuclein or tau aggregation in primary or iPSC-derived neurons and propagation of aggregates in organotypic cultures and animal models. For more information, please see:
AETIONOMY developed algorithmic approaches that allow for modeling patient-level data, enabling the identification of pathophysiological mechanisms linked to specific patient subgroups. The algorithms can be either based on unsupervised clustering approaches or bayesian network representations than include variational autoencoder neural networks to represent complex multiscale data over time. These algorithms can be used to test the prevalence of disease mechanisms in patient subgroups; future work will make pathophysiology graphs directly testable in the context of neural network representations of longitudinal patient-level (cohort) data. For more information please visit:
Procedures for federated data management
IMI have produced a framework to address challenges raised by local governance rules and potential emerging commercial and academic conflicts across the different EMIF contributing EHR databases. Such a framework will involve all database holders/organisations as participants of the EMIF horizontal layer and has the sole aim to identify governance issues of conflicts of interest that require adaptation of technical functionalities. This in turn will help build a framework focussed on enabling health care providers as well as researchers to re-use patient data in such a way it is acceptable to all partners. For more information, please visit:
Risk factors for amyloid pathology, predictors for cognitive decline: clinical biology of AD
Trial design in pre-dementia AD is challenging because subjects with pre-dementia AD are difficult to identify and limited information is available on their outcome. The lack of reliable diagnostic and prognostic markers for pre-dementia AD can be explained by the availability of only small-scale ongoing biomarker studies and longitudinal cohorts including these subjects. EMIF has linked this information and unlocked the true potential of these studies. By connecting relevant cohort studies across Europe, EMIF-AD has set up a pan-European platform for large-scale research on biomarkers and risk factors for neurodegenerative disorders. The biomarker discovery activities in EMIF-AD were driven by an extreme phenotype approach, in which decline or biomarker status was used as the end point for biomarker discovery, rather than a clinical diagnosis. Doing so, EMIF-AD has developed new treatment targets, multimodality/omics diagnostic tools and qualification level biomarker datasets suitable for presentation to regulatory authorities prior to approval for use in clinical trials and practice. Finally, prediction rules for cognitive decline in presymptomatic and prodromal AD were developed which will not only improve clinical diagnosis and prognosis, but equally support subject selection and stratification in future clinical trials. These achievements have been possible because EMIF-AD combined both large-scale patient cohorts, linkage with EHR data, and cutting edge biomarker discovery expertise. For more information, please visit:
Participant Registry in EPAD (PREPAD) tool
Creation of the EPAD register has also generated an array of software tools and processes, including the PREPAD tool for federated discovery of suitable subjects (‘Participant Registry in EPAD’). In addition, Aridhia has created a monitoring application for batch-level tracking of all pre-screening steps two databases for checking and integration of all Registry activities at the subject level (the ‘Central Archive’ and ‘Current Status’ databases), as well as custom scripts for data transformation and harmonisation. For more information, please visit:
Creation of the EPAD register has also generated an array of software tools and processes, including the DerIDIOM tool for ID encryption and matching ('DerID Input Output Management'). In addition, Aridhia has created a monitoring application for batch-level tracking of all pre-screening steps two databases for checking and integration of all Registry activities at the subject level (the ‘Central Archive’ and ‘Current Status’ databases), as well as custom scripts for data transformation and harmonisation. For more information, please visit:
VElocity for EPAD (VEEPAD) tool
Creation of the EPAD register has also generated an array of software tools and processes, including the VEEPAD tool for rapid controlled registration of high-value subjects (‘VElocity for EPAD’). In addition, Aridhia has created a monitoring application for batch-level tracking of all pre-screening steps two databases for checking and integration of all Registry activities at the subject level (the ‘Central Archive’ and ‘Current Status’ databases), as well as custom scripts for data transformation and harmonisation. For more information, please visit:
Subject Enrolment in EPAD (SEEPAD) tool
Creation of the EPAD register has also generated an array of software tools and processes, including the SEEPAD tool for semi-real-time and historical visual exploration of the Register and enrolment activities (‘Subject Enrolment in EPAD’ or SEEPAD). In addition, Aridhia has created a monitoring application for batch-level tracking of all pre-screening steps two databases for checking and integration of all Registry activities at the subject level (the ‘Central Archive’ and ‘Current Status’ databases), as well as custom scripts for data transformation and harmonisation. For more information, please visit:
Ethics work on biomarker disclosure
One of the objectives of EPAD is to investigate the ethical, legal and social implications of disclosure of biomarker results and the associated risk of AD dementia. This work has been reported in WP8 Deliverable 8.4 – Interim report on ethical and social implications of biomarker disclosure: approaches to disclosure in EPAD and in a number of scientific publications. For more information, please visit:
Procedures for trial delivery centre certification, agreement template, etc.
EPAD WP4 focuses on the selection and certification of the EPAD trial delivery centres, and the EPAD Cohort protocol early in the project, as well as the design and execution of the Proof-of-Concept (PoC) study. The team also oversees the execution of the protocols for the EPAD cohort and trials and work with National/Regional Leads and Clinical Research Organisations (CROs) on qualification, establishment and training of the EPAD trial delivery centres. For more information, please visit:
Patient engagement protocols
MOPEAD has developed specific test protocols for four models for Patient Engagement (PE) to explore two conditions (Mild AD and prodromal AD). The four MOPEAD PE models are: 1) AD Citizen Science/web-based strategy (self-administered online neuropsychological tests), 2) Open House Initiative (Neuropsychological tests at a memory clinic), 3) Primary Care (Neuropsychological tests done by GPs) and; 4) Diabetes clinics (Neuropsychological tests administered to type 2 diabetes patients at diabetes clinics). For more information please visit:
EQIPD Quality System
The EQIPD Quality System (QS) is a flexible, fit for-purpose, lean and user-friendly quality management system for non-regulated drug discovery research. It includes guidelines, procedures & a certification system for preclinical research. The objective of the EQIPD QS is to support the essential processes, procedures, responsibilities and cultural aspects relevant to implement the guiding principles that improve robustness of preclinical studies (e.g. regulatory aspects, recommendations for publications and funding applications, etc). For more information, please visit:
General information: https://eqipd-toolbox.paasp.net/wiki/Toolbox
White paper: https://osf.io/ng32b
Further information about the EQIPD Quality System (why, what and how) can also be viewed in the following 4 short videos:
EQIPD intro Part 1: Why (https://www.youtube.com/watch?v=hOaCILTwcU4)
EQIPD intro Part 2: What (https://www.youtube.com/watch?v=bK6emsX5G1Y)
EQIPD intro Part 3: How (https://www.youtube.com/watch?v=D_Wl6kcs9vU)
EQIPD intro Part 4: Why Quality Matters (https://eqipd-toolbox.paasp.net/wiki/Why_quality_matters)
Handbook of good research practice in non-clinical pharmacology and biomedicine
To disseminate aligned approaches to rigor in nonregulated applied research, academic and industry members of EQIPD have produced an open-access Handbook of Experimental Pharmacology volume dedicated to various aspects of good research practice.
For more information, please visit:
Living systematic review
EQIPD is conducting a “living” systematic review to identify universally-applicable guiding principles and criteria governing rigour in the design, conduct, analysis and reporting of preclinical neuroscience and safety research. The living systematic review screens primary research in AD, with approximately 26,000 publications identified and 13,863 papers screened so far (updated October 2019). For more information, please see:
Tools for isolating and characterising Tau & a-Synuclein, including aggregation assays
IMPRiND has optimised protocols for the isolation and characterisation of proteopathic assemblies for tau and alpha-synuclein as well as assays to measure aggregation that are suitable for screening or target validation. For more infromation, please see:
Tools and assays for targeting and analysing TREM2 & CD33
PHAGO will generate TREM2 and CD33 tools for use to the research community. These tools will include reporter cells and optimised reporter assays, suitable for further development of treatments targeting TREM2 and/or CD33 in AD. Furthermore, PHAGO will generate several iPSC lines with TREM2 and CD33 variants. For more information, please see:
EBiSC template PIS and ICF
EBiSC has a template Participant Information sheet (PIS) and Informed Consent Form (ICF) available on the website which can be openly downloaded and adapted for local use inlcuding local ethical review prior to use. Adoption of these templates simplified downstream use and ensures that all critical aspects of use for iPSC generation and explicitly and clearly covered. For more information, please visit:
Protocols on use of hiPSC lines
Simple and easily understandable protocols which outline how hiPSC lines should be thawed, cultured, monitored and cryopreserved. These are publically available via the EBiSC catalogue. For more information, please visit:
hPSCreg nomenclature tools
Registration of hPSC lines at hPSCreg allows adoption and use of standardised naming tools for donor codes and related iPSC lines. For more information, please visit:
Ethical and legal framework
EBiSC has a robust overview of the ethical and legal landscape regarding the generation and downstream use of hiPSCs. This includes an ethical advisory board and a biosample acquisition team that supports organisations who would like to deposit their lines into EBiSC and can give guidance on licensing and third party obligations which may need to be assessed. For more information, please visit:
EXAG Advisory Agreement Template
ROADMAP established the Expert Advisory Group (EXAG) to ensure the relevance and usability of ROADMAP activities and outputs to regulators and HTA agencies. For more information, please see:
ROADMAP’s Interactive Data Cube offers an overview of availability of European real-world data on Alzheimer’s disease (AD). The Data Cube can be seen as a three-dimensional ‘heat map’ to interactively visualise how European data sources capture relevant AD-related outcomes. It also provides an overview of the relevance of such outcomes for different disease stages, and for different types of stakeholders. ROADMAP’s Interactive Data Cube does not provide access to any underlying data for any of the different data sources. Its aim is to only provide high-level information about availability of such data, as provided by the data sources themselves. Interested parties should contact data sources directly. For more information, please visit:
Relevant functional outcomes for different stakeholder groups
ROADMAP identified the Alzheimer’s disease-relevant priority outcomes for different stakeholder groups (e.g. professionals working in dementia, people with dementia, caregivers) through systematic literature review, patient and public consultations, and stakeholder surveys. For more information, please see:
Research Participant Panel
EPAD has established an open dialogue with participants in the EPAD studies, giving them an active role in influencing the design, conduct and reporting of research. The research participant panel involves a small group of EPAD research participants from several European countries who participate in regular meetings to identify issues associated with participation, disclosure, consent and privacy. The Participant Panel provides feedback on the study experience, reviewing study documentation and acting as participant representatives in decision-making processes that directly affect them. For more information, please visit:
Protocols for patient engagement
MOPEAD tested and evaluated four models for Patient Engagement (PE) to explore two conditions (Mild AD and prodromal AD). The four MOPEAD PE models are: 1) AD Citizen Science/web-based strategy (self-administered online neuropsychological tests), 2) Open House Initiative (Neuropsychological tests at a memory clinic), 3) Primary Care (Neuropsychological tests done by GPs) and; 4) Diabetes clinics (Neuropsychological tests administered to type 2 diabetes patients at diabetes clinics). Each model has its own specific protocol of tests. For more information, please visit:
Patient Advisory Board
RADAR-AD has established a Patient Advisory Board (PAB) which is composed of people living with AD and AD support groups. RADAR-AD holds regular consultation sessions with the PAB, covering topics such as the feasibility and acceptability of different interventions, and the wording of participant information documents. For more information, please visit:
Patient Advisory Board
To ensure that the views of people with conditions are incorporated into RADAR-CNS we have set up a Patient Advisory Board that includes people with depression, epilepsy and multiple sclerosis along with representatives from relevant support organisations. Their role as self-employed advisors is to provide feedback on the layout and content of research materials and provide expert opinions on important decisions to be made in the design of studies. For more information, please visit:
The EPAD Academy aims to efficiently leverage EPAD resources to foster and develop academic research capacity and output in AD across Europe for maximum global impact. Mission: (1) to help create the next generation of AD researchers and thought leaders, by creating and facilitating opportunities for junior researchers’ career advancement, (2) to create fair and efficient procedures for EPAD and non-EPAD research teams to access EPAD data, samples and research participants with the objective of deepening the understanding of AD onset and progression, and the factors contributing to underlying processes and (3) to support the EPAD academic output in terms of scientific publications, participation in conferences and development of guidelines and studies, and to maximise their visibility and impact. It is led by CHUT. For more information, please visit:
Training videos on use of hiPSC lines
A collection of videos which guide users on how to practically perform thawing, culturing, monitoring and cryopreservation of hiPSC lines, according to best practice. These are available via the website. For access to SOP training videos, please reach out to email@example.com
EQIPD Training Platform
EQIPD has developed an online educational platform providing education and training in the principles and application of quality and rigour in preclinical studies, where there are currently a number of e-learning modules available (https://quality-preclinical-data.eu/learning-environment/eqipd-e-learning-modules/). In addition, as part of EQIPD’s learning environment, EQIPD organizes an annual workshop in collaboration with the ECNP Preclinical Data Network. For more information, please visit:
EQIPD Quality Label
EQIPD has developed an assessment procedure that aims to confirm a research unit’s compliance with the EQIPD expectations about research rigor and data integrity. The EQIPD Quality Label can be awarded to both organizations with fully implemented Quality System (to indicate long-term maintenance of high-quality standards) and organizations meeting key expectations about research rigor and data integrity (to indicate current adherence to high quality standards to be maintained over short period of time required for a specific project or collaboration).
For more information, please contact: firstname.lastname@example.org
A guidance for core facilities
EQIPD is developing guidance intended to support application of EQIPD quality standards in research projects involving core facilities.
For more information, please visit:
A tool to support sponsored research
EQIPD has developed a tool intended to support organizations that outsource nonregulated research activities. Using this tool, sponsors of research can select service providers based on adherence to good research practice criteria.
The tool can also be used by service providers (e.g., contract research organizations) to review various aspects of research rigor and data management that are important for the sponsors.
The tool has been successfully implemented on the Scientist.com and Science Exchange platforms, leading marketplaces for outsourced R&D activities.
(e.g., Scientist.com https://www.businesswire.com/news/home/20201201005416/en/Scientist.com-Expands-Award-Winning-Compliance-Platform-to-Include-International-Research-Consortium’s-Preclinical-Study-Standards and ScienceExchange https://blog.scienceexchange.com/2020/11/science-exchange-partners-with-joint-pharmaacademic-consortium-to-improve-research-reproducibility/).
A guidance for industry-academia collaboration
EQIPD has developed guidance intended to improve the traceability and integrity of data obtained through research as part of an academic-industry collaboration. For more information, please visit:
EQIPD has developed a Toolbox, an online wiki-based platform that intends to collect and disseminate all information (guidelines, tools, literature, web links, etc.) related to various aspects of research rigor.
The platform is open to any member of the research community to register and contribute information and resources.
new epad title here tools-clinical-epad-11
new epad content here tools-clinical-epad-11
Advanced augmented reality monitor for assessing the risk of Alzheimer and Dementia
The test is based on two augmented reality gamified tasks. In the first task virtual objects appearing on the video image captured by the device active camera will be hidden in some specific part of the room and need to be retrieved some minute afterward. A second test require to navigate through the room by watching in the images of the environment transmitted by the camera of the device while a virtual situation of danger and stress is simulated. The execution of these tests requires an active functional engagement of several cognitive dimension and is captured by the device sensors every second. The duration is typically about 15 minutes.
Daily life tasks monitoring app for cognitive status assessment (Banking App)
A smartphone Banking App has been developed by CERTH to assess parameters related to the ability of managing finances during a clinical trial in the context of Dem@Care (http://demcare.eu). The cross-border trial with 190 participants in Thessaloniki, Greece and 100 in Nice, France revealed high accuracy (more than 80%) to discriminate between healthy, MCI and AD cognitive states, while the banking app itself found statistically significant differences between the three groups in multiple parameters e.g. time to complete, fictional correct input (PIN number, account number), number of attempts etc. The app is implemented as a web application with a responsive User Interface which means it may be used on any PC, tablet or smartphone device. It simulates realistic usage of a bank ATM, prompting for PIN code, amount and account number to transfer money to, in attempt to pay the bills. Meanwhile, it measures parameters related to the disease such as number of attempts, correctness of input, duration etc. The Banking App is recommended for usage in a lab setting under guidance of professionals as an assessment (not a monitoring tool), which is its purpose in RADAR-AD.
Advanced data management dashboard for monitoring of data continuity from remote sensors
Development of RADAR-AD near real-time dashboard to establish appropriate Grafana alerts for clinical teams based on participant data status. This significantly improved design for dashboarding the data flowing through the RADAR-base has a number of advantages over previous iterations.
TREM2 cleavage modulators and uses thereof
This asset relates to a binding molecule having a binding site within the ectodomain of the triggering receptor expressed on myeloid cells 2 (TREM2), wherein the binding molecule inhibits TREM2 cleavage. This binding molecule is particularly useful for treating and/or preventing a neurological disorder, such as a neurodegenerative disorder. Also encompassed by this asset is a pharmaceutical composition for use in treating and/or preventing a neurological disorder, wherein the pharmaceutical composition comprises the binding molecule of the asset.
Neurodegenerative disorders that may be treated and/or prevented by using the binding molecule of this asset include Alzheimer's disease (AD), Frontotemporal lobar degeneration (FTLD), FTLD-like syndrome, Parkinson's disease, Nasu-Hakola disease, Multiple sclerosis (MS), Huntington disease, immune-mediated neuropathies, or Amyotrophic lateral sclerosis (ALS).
Advanced passive remote monitoring (pRMT) application for user behavior modelling.
Current pRMT app from RADAR-base collects sensor data, such as number/duration of incoming/outgoing calls, caller ID; number/length of incoming/outgoing SMS.
Manual data upload tool for remote monitoring sensors data acquisition files.
The RADAR-base platform was developed in the framework of the IMI RADAR-CNS project and provides an end-to-end solution to collect, manage, store and visualize sensor data from smartphones and wearable devices to enable remote monitoring of study participants and decentralized clinical trials. The platform supports multiple devices for passive data collection as well as surveys and questionnaires for active participants feedback. The following data streams can be collected from smartphone sensors: Relative location, Acceleration, Gyration, Magnetic field, Step count, Light, Phone interaction status, Application usage, Bluetooth devices, Battery level. Depending on the connected wearable devices, a wide range of data streams can be collected, e.g. Acceleration, Heart rate, Electrodermal activity, Temperature, Sleep and Physical Activity.
Mezurio - A smartphone app supporting active participation in research studies and clinical trials
Mezurio is a smartphone app developed through a pre-competitive collaboration between industry (Lilly & Roche) and academia (University of Oxford), based on the very earliest neural and cognitive correlates of preclinical Alzheimer's disease (AD), utilising both active and passive data collection, and which is open and freely available to scientists. Emphasis has been placed on designing interactive experiences, which participants find engaging, thus enabling repeat, remote measurement in a little-but-often format over extensive periods. Participants interact with the app for no more than 10 minutes at a regular time of their own choosing, during each day of the study. They complete a mix of gamified tasks and short self-report questionnaire measures. The tasks cover ecologically valid measure of the kinds of complex cognition required for activities of daily living, including episodic, semantic, and spatial memory over real-world durations, executive components of attention and planning, verbal story telling tasks which test free-recall and fluency. The difficulty of each task adapts to the participants’ own abilities. Finally, the participants will be asked to install and use a keyboard dynamics module.
Defining an asset
In order to consistently build the asset map across all IMI neurodegeneration projects, NEURONET has agreed on a common definition of what an asset is.
- Existence. An asset must exist. It cannot be a planned or future outcome, or something that no longer exists (e.g. a cohort that existed but is not actively being followed up after project completion)
- Specificity. Assets need to be concrete, not a category of results or an abstract description. E.g. “Body of publications” would not be considered an asset.
- Tangibility. Data sets, tools, guidelines, a white paper, software, etc. can be considered assets if they can be accessed, incorporated, consulted, or leveraged in some way. "Expertise in XYZ" in general is not tangible, therefore not considered an asset. Also, if a research outcome is not accessible at all, it may not be considered an asset either, as it would not meet the usefulness criteria described below. On the other hand, a site network would meet the tangibility criteria if they use common practices, team dynamics, common protocols, etc.
- Re-usability. Assets should be amenable for re-use by others. If something is so ad hoc that it can only be useful for the originating project, it may not be considered an asset.
- Provenance. Assets need to be defined by basic parameters such as description, ownership, authorship, location (link for example), access/use conditions, etc. in sufficient detail. If this information is unknown, the asset may not be incorporated into the asset map, as assessment of some of the other criteria would not be possible.