In order to avoid the situation where two investigators study the same research question, please search our database to determine if your topic has already been studied. If you find that your topic or a related topic has already been submitted, you may wish to contact the investigator to inquire about his/her findings to determine how you might proceed. You may wish to collaborate or modify your request to avoid overlap. The results below reflect requests made since online requests have been accepted. As such, not all fields will have data as certain information, such as aims, were not collected until recently. If an entry has been assigned an ID # (e.g. TU1004), the full request has been submitted and is either approved, disapproved or in process.
Investigator: Yi Su
Title: Tracer harmonization for amyloid and tau PET imaging using statistical and deep learning techniques
Date of Request: January 24, 2025
Status:
ID:
Aim 1: to develop deep learning models that can generate imputed amyloid PET images of one tracer based on the images from another tracer.
Aim 2: to develop statistical learning approaches that can generate harmonized amyloid burden measurements.
Aim 3: to validate statistical and deep learning approaches to the harmonization of tau PET imaging data.
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Investigator: Tammie L.S. Benzinger
Title: Monitoring of Amyloid-Related Imaging Abnormalities in Monoclonal Antibody Therapy Using Generalized Diffusion Basis Spectrum Imaging (g-DBSI):
Date of Request: January 17, 2025
Status:
ID:
Aim 1: Quantify neuroinflammation and vasogenic edema associated with Amyloid Related Imaging Abnormality (ARIA) during monoclonal antibody (mAb) therapy
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Investigator: Professor Michael Barnett (biosketch attached)
Title: CAA and Amyloid Related Imaging Abnormalities (ARIA): automated quantitation and clinical predictors
Date of Request: January 9, 2025
Status:
ID:
Aim 1: Develop deep-learning based algorithms for the automated detection and quantification (severity) of ARIA including CAA in the model
Aim 2: Investigate the association between cerebrospinal fluid (CSF) and blood neurofilament light (Nfl) levels, mutation type and the risk, development and progression of ARIA in relation to CAA
Aim 3: Integrate CAA/ARIA algorithms with an existing clinical tool for automated AI-based quantitation of brain structures in subjects with Alzheimer disease.
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Investigator: None
Title: Japan Webinar Deck 11th December
Date of Request: December 9, 2024
Status:
ID:
Aim 1: We are using the images for a webinar to be held in Japan on 11 December. The images will be used for the presentation shown during the webinar.
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Investigator: Dr. Hongxia Xu
Title: On CSF biomarker screening in patients with Alzheimer’s disease
Date of Request: November 19, 2024
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ID:
Aim 1: It is hoped that the complete CSF proteomics data will be used to screen for new, usable drug targets. It brings new perspectives for the treatment of AD patients.
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Investigator: null
Title: To explore the causal relationship between gut microbiota and Alzheimer’s disease (AD) by Mendelian randomization
Date of Request: October 29, 2024
Status:
ID:
Aim 1: To explore the causal relationship between gut microbiota and Alzheimer’s disease through Mendelian randomization, and write corresponding papers for journal publication
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Investigator: Yi Su
Title: Tracer harmonization for amyloid and tau PET imaging using statistical and deep learning techniques
Date of Request: September 28, 2024
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ID:
Aim 1: Explore harmonization of different tau tracers
Aim 2: Explore harmonization of different tau tracers
Aim 3: Explore impact of mixing tracers in clinical trials
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Investigator: Jorge J Llibre Guerra
Title: Developing Predictive and Diagnostic Biomarkers for Amyloid-Related Imaging Abnormalities.
Date of Request: September 28, 2024
Status:
ID:
Aim 1: Aim 1: Evaluate the Impact of ARIA on Clinical-Cognitive Performance and Treatment Outcomes.
Aim 2: Aim 2: Identify Clinical, Genetic, and Biomarker Predictors of ARIA Risk in Alzheimer’s Disease.
Aim 3: Aim 3: Develop Biomarkers for ARIA occurrence and resolution in Alzheimer’s Disease.
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Investigator: Alexandre Bousse
Title: Plug-and-play PET reconstruction
Date of Request: September 24, 2024
Status:
ID:
Aim 1: Enhancing the quality of low-count PET images through a novel reconstruction method
Aim 2: Reducing patient dose and improving diagnostic
Aim 3: Proposing an AI-based reconstruction method with theoretical guarantees
Aim 4: Validation our method on two real patient data
Investigator: Alexandre Bousse
Title: Plug-and-play PET reconstruction
Date of Request: September 22, 2024
Status:
ID:
Aim 1: Enhancing the quality of low-count PET images through a novel reconstruction method
Aim 2: Reducing patient dose and improving diagnostic
Aim 3: Proposing an AI-based reconstruction method with theoretical guarantees
Aim 4: Validation our method on two real patient data
Investigator: Andrew Aschenbrenner
Title: Establishing the utility and sensitivity of high-frequency cognitive assessments in Dominantly Inherited Alzheimer Disease.
Date of Request: June 28, 2024
Status:
ID:
Aim 1: To quantify the cognitive effects of ADAD mutations, APOE genotype and AD biomarkers using a high-frequency cognitive assessment (HFCA) paradigm, the Ambulatory Research in Cognition (ARC) smartphone application.
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Investigator: NA
Title: Disappearing ARIA-H Microhemorrhages
Date of Request: June 27, 2024
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ID:
Aim 1: Demonstrate that ARIA-H microhemorrhages may resolve, rather than persist over time
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Investigator: Klaus Romero
Title: Model-informed drug development (MIDD) in Autosomal Dominant Alzheimer’s Disease
Date of Request: May 31, 2024
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ID:
Aim 1: Our goal is to develop a comprehensive drug-disease-trial model across the entire disease continuum of Autosomal Dominant Alzheimer’s Disease (ADAD). The drug-disease trial will serve as the foundation for a clinical trial simulation tool for ADAD
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Investigator: NA
Title: Alzheimer’s Disease Clinical Trials: What have we learned from magnetic resonance imaging
Date of Request: February 6, 2024
Status:
ID:
Aim 1: outline how MRI is used in eligibility and safety monitoring in AD clinical trials
Aim 2: review use of advanced MR imaging techniques in AD clinical trials
Aim 3: discuss opportunities for acceleration in MRI trial protocols
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Investigator: NA
Title: Alzheimer’s Disease Anti-Amyloid Immunotherapies: Imaging Recommendations and Practice Considerations for ARIA Monitoring
Date of Request: February 6, 2024
Status:
ID:
Aim 1: Review key MRI sequences for ARIA monitoring
Aim 2: Provide imaging recommendations for clinical practice
Aim 3: Highlight role of the radiologist in identifying and communicating ARIA findings
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Investigator: jing zhang
Title: Research on the value of multi-layer network characteristics in the brain of patients with early-onset AD in disease diagnosis
Date of Request: January 6, 2024
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ID:
Aim 1: Exploring the changes in multi-layer network characteristics of the brain in patients with early-onset AD
Aim 2: Explore the value of multi-layer network features in disease diagnosis
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Investigator: Aschenbrenner
Title: Quantifying the impact of ARIA on cognition measured with computerized testing.
Date of Request: November 9, 2023
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ID:
Aim 1: Determine if ARIA produces measurable effects on cognition and quantify the effect size.
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Investigator: Jorge J Llibre Guerra & Clara Vila-Castelar
Title: Influence of biological sex in response to treatment in Autosomal Dominant Alzheimer’s Disease
Date of Request: October 27, 2023
Status:
ID:
Aim 1: To describe sex differences in cognitive outcomes between women and men
Aim 2: To investigate possible differences in PiB-PET, brain glucose metabolism, and structural atrophy rate of change between women and men.
Aim 3: To compare fluid biomarker levels and rates of change between women and men in DIAN-TU double blind period of gantenerumab or solanezumab.
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Investigator: Colin Masters
Title: Automated detection and reporting of amyloid-related imaging abnormalities (ARIA) with emerging Alzheimer’s disease therapeutics
Date of Request: October 12, 2023
Status:
ID:
Aim 1: To develop automated machine learning algorithms for detection and reporting of ARIA using serial MRI scans of patients who underwent treatment with an anti-Aβ antibody therapy.
Aim 2: To identify the potential AD biomarkers that are associated with an increased risk of ARIA development.
Aim 3: Determine the level of autoantibodies to Abeta in the baseline and follow up plasma who are being treated with an anti-Abeta antibody therapy.
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Investigator: NA
Title: Review of ARIA in Japanese
Date of Request: October 2, 2023
Status:
ID:
Aim 1: We want to use DIAN’s images from an article in our review article
Aim 2: We want to use the images to illustrate actual symptoms
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Investigator: Laurent Roybon
Title: Models and therapies for Dominantly Inherited Alzheimer disease
Date of Request: August 16, 2023
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ID:
Aim 1: Generate humanized models of early and advanced AD cellular pathogenesis
Aim 2: Use humanized models to explore a gene therapy for disease progression in AD
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Investigator: Randall Bateman
Title: Proteomic Biomarkers in Autosomal Dominant Alzheimer’s Disease
Date of Request: August 7, 2023
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ID:
Aim 1: Define the landscape and temporal sequence of CSF and plasma proteomic changes in ADAD
Aim 2: Determine how treatment with anti-amyloid immunotherapies affects levels of brain-based biomarkers in ADAD CSF and plasma
Aim 3: Leverage proteomics data to provide biological pathway and systems context to experimental results generated in other DIAN projects
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Investigator: Junie Saint Clair
Title: Examining the Predictive Value of Synaptic Dysfunction and Neuronal Injury Measures on Imaging Markers of Disease Presentation and Progression in Alzheimer’s Disease
Date of Request: August 1, 2023
Status:
ID:
Aim 1: Evaluate association between rates of longitudinal change in CSF levels of Ng, SNAP-25, VILIP-1 and imaging brain changes and cognition in a DIAD cohort.
Aim 2: Evaluate association between rates of longitudinal change in CSF levels of Ng, SNAP-25, VILIP-1 and imaging brain changes and cognition in aged adults LOAD cohort.
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Investigator: Bart De Strooper
Title: Testing the role of presenilins in cell states
Date of Request: April 14, 2023
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ID:
Aim 1: Profiling the gamma-secretase substrate proteome in PSEN1 H163R iPSC-derived microglia
Aim 2: Characterizing the transcriptional and functional phenotype of human PSEN1 H163R microglia in a humanized chimeric AD mouse model.
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Investigator: Carlos Cruchaga
Title: Functional characterization of brain circular RNAs in Alzheimer disease using induced pluripotent stem cell models
Date of Request: April 4, 2023
Status:
ID:
Aim 1: To analyze the role of circHOMER1 in AD-related molecular phenotypes using cellular models
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Investigator: RANDALL J BATEMAN
Title: DIAN-TU-001 Clinical Core Statistical Analysis Plan (SAP) for biochemical measures of amyloid and tau phosphorylation in the brain, and their correlation with clinical, cognitive, and other imaging/CSF outcomes
Date of Request: January 17, 2023
Status:
ID:
Aim 1: Specific Aim 1: To biochemically quantify the amount of soluble and insoluble amyloid-beta and tau species in specific regions of the frozen brain regions by mass spectrometry in DIAN-TU, DIAN-Obs and non-AD age-matched controls. Additional biochemical measures of other biomolecules, for example, alpha synuclein, APP, ApoE, inflammatory markers, synaptic & neuronal markers will also be explored.
Aim 2: Specific Aim 2: Compare the amounts of soluble and insoluble amyloid-beta and tau species between active gantenerumab, active solanezumab, placebo (those from the DIAN-TU placebo arm who did not continue in the gantenerumab Open Label Extension, when available), and control cases (including DIAN-Obs and non-AD controls) to determine effects of drug treatment on amyloid-beta and tau species. Active drug data will be compared with placebo and controls, not with other drug data.
Aim 3: Specific Aim 3: To quantify by immunohistochemistry the amount of amyloid-beta deposition, tau pathology, astrocytosis, microgliosis, alpha-synucleinopathy, and TDP-43 proteinopathy in multiple neuroanatomic regions of the formalin-fixed brain tissue samples from DIAN-TU and DIAN-Obs participants and their family members, and non-AD age-matched controls. Additional immunohistochemistry measures of other biomolecules, for example, APP, ApoE, inflammatory markers, synaptic & neuronal markers will also be explored.
Aim 4: Specific Aim 4: Evaluate how amyloid-beta and tau species in insoluble and soluble fractions of the brain and pathologic features measured by immunohistochemistry in formalin-fixed brain tissue are correlated with each other, as well as with the cross-sectional value and longitudinal changes in other imaging/CSF biomarkers (e.g., amyloid PET, tau PET, CSF amyloid-beta, total tau, and phospho-tau), and with clinical and cognitive outcomes, and how these correlations are altered by the active treatments.
Investigator: Tammie Benzinger
Title: Quantification of Neuroinflammation in Autosomal Dominant Alzheimer’s Disease Using Small-block Brain Specimen imaged by Diffusion Basis Spectrum Imaging (DBSI)
Date of Request: August 16, 2022
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ID:
Aim 1: assess the value of DBSI for the study of ADAD by comparing post-mortem MRI signals with histologic data
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Investigator: David Gate
Title: Comparing active and passive Abeta vaccination by spatial transcriptomics
Date of Request: July 25, 2022
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ID:
Aim 1: Identify spatial transcriptomic changes associated with Aβ vaccination.
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Investigator: Jinlong Yu
Title: Install APP A673T mutation for treatment of AD
Date of Request: May 20, 2022
Status:
ID: DR_022
Aim 1: To optimize the base editor condition in AD patients IPSC derived neurons.
Aim 2: Test if the additional E674K mutation base editing introduced modulates the Aβ peptides production and Aβ peptides ‘s toxicity
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Investigator: Ifrah zawar
Title: Csf biomarkers in seizures among AD patients
Date of Request: April 11, 2022
Status: Closed
ID: DR_020
Aim 1: To study the differences in csf biomarkers in AD patients with and without seizures
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Investigator: Bateman/Benzinger
Title: ASNR White Paper on ARIA
Date of Request: February 8, 2022
Status:
ID:
Aim 1: Training of Radiologists and Neuroradiologists
Aim 2: Enhance physician understanding of ARIA in order to improve detection and reporting. Additionally, the objective is to provide physicians with imaging examples of the severity grading of ARIA as well as pointing out potential pitfalls in interpretation
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Investigator: Giuseppina Tesco
Title: Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
Date of Request: January 24, 2022
Status: Referred to Obs
ID:
Aim 1: Study of endolysosomal alterations (including exosomes) in brain cells cultures derived from fDA iPSC lines and isogenic controls
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Investigator: Colin Masters
Title: CSF Abeta42 and p-tau level review
Date of Request: December 8, 2021
Status:
ID: DR_018
Aim 1: To provide further information regarding ex-participant 3031007’s mutation and pathogenic status. V2 28 May15 CSF Abeta42 and p-tau levels to be reviewed.
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Investigator: Jan Torleif Pedersen, PhD MSc
Title: Investigation of pS396-tau in samples from DIAN-TU biobank
Date of Request: December 3, 2021
Status: Referred to Obs
ID: DR_017
Aim 1: To investigate pS396-tau levels in CSF samples from DIAN-TU
Aim 2: To investigate pT217-tau levels in CSF samples from DIAN-TU
Aim 3: To establish potential correlation between pS396-tau, pT217-Tau and clinical progression parameters
Aim 4: To investigate tau species in post-mortem brain material targeted by Lu AF87908
Investigator: Antonio Boza-Serrano
Title: Galectin-3 as a prognostic biomarker to monitor Autosomal dominant Alzheimer Disease’s progression and response to gantenerumab.
Date of Request: October 29, 2021
Status: Pending
ID: DR_015
Aim 1: To evaluate if gal3 levels in ADAD samples might track /monitor the progression of AD pathology and whether or not gal3 levels are altered under the different treatment evaluated with the patients (gantenerumab)
Aim 2: To compare the levels of gal3 with the classic biomarkers of pathology progression (amyloid-beta 42, total tau, p-tau181, NfL and PIB-Pet) evaluated in CSF and serum over the DIAN-TU study in placebo, ganterenumab treated patients.
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Investigator: Ron Davis
Title: Unraveling the complexity of mitochondrial pathology in familial Alzheimer’s disease
Date of Request: September 14, 2021
Status: Referred to Obs
ID: DR_014
Aim 1: Use high-content and high-throughput assay to quantify the MT dynamics phenotypes that develop in neurons derived from iPSCs of fAD subjects and age-matched and/or isogenic controls.
Aim 2: Define the functional impairment in these neurons (IMM-inner mitochondrial membrane potential).
Aim 3: Interrogate the function of the electron transport chain (ETC) in these neurons.
Aim 4: Measure the structural integrity of MT, the ETC, and MT-related processes in these neurons by quantitative Western blotting of proteins and/or tandem mass tag quantitative mass spectroscopy.
Investigator: N/A
Title: Relationship between regional baseline and longitudinal tau PET SUVR, and correlations with change in cognition in participants from the DIAN-TU study
Date of Request: July 19, 2021
Status: Approved
ID: DR_013
Aim 1: Characterize the spatial patterns of tau deposition at baseline and over time in the DIAD population
Aim 2: Estimate the rate of change in tau deposition in DIAD participants in each of the provided parcellated brain regions
Aim 3: Identify the (meta)ROI(s) at baseline that best correlate with change in tau PET SUVR and change in cognition, respectively, over time
Aim 4: Characterize the relationship between change in tau PET SUVR and change in cognition (and other biomarkers)
Investigator: Mariah S. Hahn
Title: Targeting Dysregulated Synapse and Proteostasis Mechanisms in Alzheimer’s Disease
Date of Request: June 1, 2021
Status: Referred to Obs
ID: DR_012
Aim 1: Develop a 3D culture system compatible with long-term (>3 month) iNeuron culture, extension, synapse formation and elimination, and quantitative assessment of neural circuit activity using “healthy” networks.
Aim 2: Compare AD_(PSEN1)-iNeuron cultures to iNeuron cultures derived from unaffected family member controls with respect to Aβ, tau phosphorylation, synapse maintenance and proteostasis.
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Investigator: Yan Li
Title: Gain Precision on the Measurement of Cognitive Impairment – Item Response Theory Scoring of the CDR
Date of Request: May 11, 2021
Status: Pending
ID: DR_011
Aim 1: Evaluate the difficulty and discrimination level, and the longitudinal change of each item in CDR and their longitudinal change over time
Aim 2: Develop the best fitting item response theory (IRT) model for automatically scoring dementia severity (IRT score)
Aim 3: Compare the performance of the IRT score with that of the CDR sum of box in terms of powering a clinical trial and precision in tracking cognitive change over time, especially for cognitively normal participants
Aim 4: Valid the performance of the IRT score using other psychometric measures and biomarkers.
Investigator: Suman Jayadev
Title: Peripheral immune profiles in ADAD
Date of Request: April 20, 2021
Status: Pending
ID: DR_016
Aim 1: Measure immune related microRNA, exosome, proteins in carriers and non-carriers
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Investigator: NA
Title: Proposal for comparison between Dominantly Inherited Alzheimer Disease and sporadic early-onset Alzheimer’s disease
Date of Request: May 20, 2020
Status: Pending
ID: DR_002
Aim 1: To compare clinical presentation, neuropsychological performance and cognitive decline rate between DIAD and sporadic EOAD
Aim 2: To examine in vivo the regional distribution of tau, amyloid-beta, brain glucose metabolism, and structural atrophy, as well as their relationships, in DIAD and sporadic EOAD
Aim 3: To compare CSF biomarkers levels and rates of change in DIAN and sporadic EOAD
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Investigator: NA
Title: Imaging-Histology Comparisons of Tau Pathology in ADAD and LOAD
Date of Request: April 21, 2020
Status: Approved
ID: DR_001
Aim 1: Perform a quantitative comparison of tau pathology in ADAD and LOAD using imaging and histology
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