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, 756 research participants and 543 scans performed (Last update May 2020). For more details please visit: https://amypad.eu/project/dpms/

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 17 active sites, 5 parent cohorts, 572 research participants and 405 scans performed (Last update May 2020). For more details please visit: https://amypad.eu/project/amypad-pnhs/

wThe EPAD LCS is an prospective, multicentre, pan-European longitudinal cohort study. Participants were 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. Inclusion of the last participant in the LCS took place in March 2020. There were a totral of 2.094 screened research participants in the LCS. The LCS is led by University of Edinburgh, for more information please visit http://ep-ad.org/.

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. 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: http://www.emif.eu/emif-ad-2/

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 MEEG (n=92) scans have been collected. In addition skin biopsies (n=99) and ultrasound of the carotid artery (n=102) are also available. The first annual follow-up measurements have completed in n=129 as of November 2019, with plans for a second annual follow-up in 2020. Data requests can be submitted via the EMIF-AD catalogue. For more information please visit: http://www.emif.eu/emif-ad-2/

The EMIF-AD PreclinAD study aimed to identify new risk factors and diagnostic markers for both amyloid pathology and cognitive decline in cognitively normal subjects with or without amyloid pathology. Monozygotic twin pairs were included such that genetic and environmental pathways could 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), a blood collection (n=192) and a 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: http://www.emif.eu/emif-ad-2/

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: https://www.medrxiv.org/content/10.1101/19004804v2.full.pdf

The EMIF-Platform has leveraged data on more than 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 http://www.emif.eu/emif-catalogue/

IM2PACT will identify candidate genes or pathways 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.

EQIPD has obtained study reports for historical data from EFPIA partners, CROs and academic labs, and has calculated 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.

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.

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.

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.

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).

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. Two datasets are currently available: V500.0 published 19th May 2019 - (doi:10.34688/epadlcs_v500.0_19.05.10) and V1500.0 published 29th November 2019 (doi:10.34688/epadlcs_v1500.0_19.11.29). For more information, please visit: http://ep-ad.org/erap/.
 

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: https://amypad.eu/data/

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: https://emif-catalogue.eu/

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: https://www.medrxiv.org/content/10.1101/19004804v2.full.pdf AETIONOMY datasets are available via request to Jean-Christophe Corvol at the ICM in Paris.

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, see here: https://www.radar-ad.org/our-research/our-scientific-approach

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: https://www.medrxiv.org/content/10.1101/19004804v2.full.pdf

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.

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.

The EPAD LCS is an prospective, multicentre, pan-European longitudinal cohort study. Participants were 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). Further information can be found here: https://bmjopen.bmj.com/content/8/12/e021017

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: http://www.emif.eu/emif-ad-2/.

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 in 2020. Biological samples collected are as follows: 104 blood samples, 99 skin biopsies and 36 samples of CSF. For more information please visit: http://www.emif.eu/emif-ad-2/.

The EMIF-AD PreclinAD study aimed to identify 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. http://www.emif.eu/emif-ad-2/

EQIPD has developed an online educational platform providing certified 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 organises a Summer School (4-day training programme) every year at Radboud University Medical Center in Nijmegen (https://quality-preclinical-data.eu/learning-environment/summer-school/).

AETIONOMY’s Knowledge Base (AKB) is the unification point of the knowledge and data management on Neurodegeneration with a main focus on Alzheimer’s and Parkinson’s diseases. It includes comprehensive overviews on specific public, clinical and OMICS indices relevant to Neurodegeneration; values for such indices at retrospective and prospective studies available at different sites; and available OMICS Data. https://data.aetionomy.scai.fraunhofer.de/

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. http://neurommsig.scai.fraunhofer.de/

PHAGO will create a knowledge base infrastructure with a user-friendly search interface. The platform will contain PHAGO omics data and data sets from several public available sources. The focus will primarily be on transcriptomics.

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. A total of 46 sites have been certified and 31 of them have been opened to recruitment. The TDCs that are part of the TDC network have been certified and approved by the Chief Investigator (CI) & the Sponsor (UEDIN). For more details please visit http://ep-ad.org/.

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 further details please read WP3 project deliverables, available from http://ep-ad.org/about/publications/ and publications: https://doi.org/10.1016/j.jalz.2018.02.010 or visit http://ep-ad.org/for-intervention-owners/the-epad-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 epad.poc@ed.ac.uk. For more information please visit http://ep-ad.org/for-intervention-owners/epad-benefits/.

 

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: http://www.emif.eu/emif-in-practice/ and https://emif-catalogue.eu

 

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).

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.

Tools will be listed on the PHAGO webpage www.phago.eu and are available from the respective partner or the EBiSC Stem Cell Bank‎.

IMPRiND has optimised protocols for the isoaltion 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.

The PREPAD tool was created as part of the EPAD register and enables the federated discovery of suitable subjects (PREPAD = ‘Participant Registry in EPAD’). 

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'). 

The VEEPAD tool, which was created as part of the EPAD Register, enables the rapid, controlled registration of high-value subjects (‘VElocity for EPAD’). 

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.

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, all available from http://ep-ad.org/about/publications/.

http://ep-ad.org/mdocs-posts/wp8-deliverable-d8-4-interim-report-on-ethical-and-social-implications-of-biomarker-disclosure-approaches-to-disclosure-in-epad/
http://ep-ad.org/about/publications/

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. The outputs produced by WP4 activities have been published as project deliverables and are available on http://ep-ad.org/about/publications/.

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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.

Khanna, S., Domingo-Fernández, D., Iyappan, A., Emon, M. A., Hofmann-Apitius, M., & Fröhlich, H. (2018). Using multi-scale genetic, neuroimaging and clinical data for predicting alzheimer’s disease and reconstruction of relevant biological mechanisms. Scientific reports, 8(1), 1-13. https://www.nature.com/articles/s41598-018-29433-3

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).

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.
Tool: https://datacube.roadmap-alzheimer.org/
Publication: https://www.sciencedirect.com/science/article/abs/pii/S1552526019354871

A combination of wearables and smartphone-based RMTs will collect data on function, mood, executive function and cognition actively and passively.

ROADMAP established the Expert Advisory Group (EXAG) to ensure the relevance and usability of ROADMAP activities and outputs to regulators and HTA agencies.

https://kb.imi-neuronet.org/admin/documents/10

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 http://ep-ad.org/.

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.

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.

IM2PACT will increase our understanding of the BBB both in health and disease, characterising BBB transport mechanisms and developing innovative and effective brain delivery systems.

EQIPD has defined the variables in study design and data analysis that influence outcome in preclinical neuroscience (focus on Alzheimer’s disease and psychosis) and (neuro-)safety studies. These variables and other preclinical research guidelines have been published in the Springer "Handbook of good research practice in non-clinical pharmacology and biomedicine", available here: https://rd.springer.com/book/10.1007/978-3-030-33656-1

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 further details please read the published protocol: http://dx.doi.org/10.1136/bmjos-2018-000004.

The main goal of PHAGO is to understand the function of TREM2, CD33 and related pathways in AD, so that they can be targeted to treat the disease.  Publications of Phago can be found here: https://www.phago.eu/publications/

The APOE gene is a well-known risk factor for developing Alzheimer's disease (AD), but precisely how this gene contributes to the risk of developing AD is not known. People who carry the APOE4 version of the gene have a considerably higher risk of developing AD. They also tend to develop the disease much earlier in life. However, the reasons for this are not well understood and therefore APOE has largely been ignored in the quest to find treatments for AD. ADAPTED will increase our insights into one of the key molecular causes of AD, something that will in turn lead to better treatments for patients.

AETIONOMY paved the way towards a new approach to the classification of neurodegenerative diseases focussing on Alzheimer's and Parkinson's diseases, deriving as a result the prototype of a new mechanism-based taxonomy. This increases the probability of successfully discovering and developing new therapies for neurodegeneration, and thereby increasing patients' chances of receiving treatments that are effective.

IMPRiND will improve our understaning of mechanisms that influence protein aggregation via the completion of a number of genetic screens. These will map pathways and modifiers that could be harnessed for the assessment of novel drug targets

Dementia researchers are increasingly focusing their efforts on finding ways to prevent the onset of dementia symptoms in the first place, and for this they need to work with people who are still in the very earliest stages of the disease. The MOPEAD project aimed to identify and test different models for engaging with this important group and determine which models work best in different situations. As well as adding to our understanding of the earliest stages of dementia, the knowledge generated by MOPEAD will facilitate recruitment for clinical trials and, most importantly, ensure that patients are able to access support from early on in their disease.

EPAD is a Europe-wide collaboration aiming to improve the understanding of the early stages of Alzheimer’s disease. It combines knowledge and expertise from 39 organisations across multiple sectors from academia and industry, bringing together a wealth of experience to its activities and making it the largest ever public-private partnership in Alzheimer’s disease research. For more information please check the project publications on http://ep-ad.org/about/publications/.

AMYPAD aims to improve the understanding, diagnosis and management of Alzheimer’s disease through the utilisation of ß-amyloid PET imaging. The specific aims of the study are: 1) to improve the diagnostic work-up of people suspected to have Alzheimer’s disease and their management; 2) to understand the natural history of the disease in a pre-symptomatic stage; and 3) to select people for treatment trials aiming at preventing Alzheimer’s disease.

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.

http://www.emif.eu/emif-ad-2/

People in the earliest stages of Alzheimer’s disease experience declining cognitive and functional abilities, making it harder for them to remember things and places, carry out simple calculations, use a phone/computer, drive, and adhere to medications. RADAR-AD's digital platform will draw on smartphone, wearable and home-based digital technologies to track subtle changes in the cognitive and functional abilities of people with Alzheimer’s disease.

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 details please read the following project deliverable (https://roadmap-alzheimer.org/wp-content/uploads/2018/09/D8.4_Ethics_Outcome_Prioritisation_v1_10.09.18.pdf) and publication (https://www.sciencedirect.com/science/article/abs/pii/S1552526019354871)

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.

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).

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.

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.

https://data.aetionomy.scai.fraunhofer.de/mechanistic-disease-hypotheses

AMYPAD will establish predictors of decline by using quantitative baseline and longitudinal PET measurements and determine how this can be best used to plan and monitor treatment (WP5).

EQIPD will establish an ontology for describing animal experiments, in compliance with FAIR data principles.

The EPAD Academy aims to 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 details please visit http://ep-ad.org/epad-academy/.