Ron Building
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: 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
Aim 3:
Aim 4:
Investigator: Laurent Roybon
Title: Models and therapies for Dominantly Inherited Alzheimer disease
Date of Request: August 16, 2023
Status:
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
Aim 3:
Aim 4:
Investigator: Randall Bateman
Title: Proteomic Biomarkers in Autosomal Dominant Alzheimer’s Disease
Date of Request: August 7, 2023
Status:
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
Aim 4:
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.
Aim 3:
Aim 4:
Investigator: Bart De Strooper
Title: Testing the role of presenilins in cell states
Date of Request: April 14, 2023
Status:
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.
Aim 3:
Aim 4:
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
Aim 2:
Aim 3:
Aim 4:
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
Status:
ID:
Aim 1: assess the value of DBSI for the study of ADAD by comparing post-mortem MRI signals with histologic data
Aim 2:
Aim 3:
Aim 4:
Investigator: David Gate
Title: Comparing active and passive Abeta vaccination by spatial transcriptomics
Date of Request: July 25, 2022
Status:
ID:
Aim 1: Identify spatial transcriptomic changes associated with Aβ vaccination.
Aim 2:
Aim 3:
Aim 4:
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
Aim 3:
Aim 4:
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
Aim 2:
Aim 3:
Aim 4:
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
Aim 3:
Aim 4:
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
Aim 2:
Aim 3:
Aim 4:
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.
Aim 2:
Aim 3:
Aim 4:
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.
Aim 3:
Aim 4:
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.
Aim 3:
Aim 4:
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
Aim 2:
Aim 3:
Aim 4:
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
Aim 4:
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
Aim 2:
Aim 3:
Aim 4: