Search DIAN Data Resource Requests

Title:Biogen-DIAN-TU BIIB080 Design

Date of Request:11/20/2024

Aim 1:Patient characteristics of preclinical AD with EYO -10 to +10, including (but not limited to): % amyloid positive, baseline characteristics (especially baseline tau PET), rate of change in tau PET and CDR-SB;

Aim 2:How is tau PET composite derived; If we were to include plasma p-tau enrichment, what would be the threshold?

Aim 3:Sample size calculation and assumptions for 2 year and 1 year tau PET assessment If we were to combine both DIAN and sporadic AD for this preclinical study, what would be the assumptions and sample size?

Title:Identify proteins associated with integrated biological and clinical staging using the ADRC and DIAN cohorts

Date of Request:11/01/2024

Status:pending approval

ID:DIAN-D2434

Aim 1:Identify proteins associated with integrated biological and clinical staging using DIAN cohort.

Aim 2:Test if the identified proteins in Aim1 are associated with the cortical thickness and hippocampal volume.

Aim 3:Examine function pathways for the proteins identified in Aim1.

Title:Cortical asymmetry as a tool to monitor individuals with Autosomal Dominant Alzheimer’s Disease progression

Date of Request:10/10/2024

Status:approved

ID:DIAN-D2433

Aim 1:To evaluate brain asymmetry using the Cortical Asymmetry Index in a cohort of both symptomatic and asymptomatic Autosomal dominantly inherited Alzheimer’s disease mutation carriers

Aim 2:To estimate longitudinal cortical asymmetry changes in ADAD and to evaluate cortical asymmetry as a tool to study Alzheimer’s disease progression

Title:Leveraging proteomics to identify γ-secretase-dependent pathways and changes in BBB function that drive ADAD

Date of Request:09/25/2024

Status:pending approval

ID:DIAN-D2432

Aim 1:Establish plasma and CSF proteomic signatures related to variant-specific gamma-secretase function/Aβ proteoform production.

Aim 2:Characterize changes in correlation between CSF and plasma proteins in order to develop and validate proteomics-derived markers of BBB integrity in ADAD.

Title:Tracer harmonization for amyloid and tau PET imaging using statistical and deep learning techniques

Date of Request:09/25/2024

Status:approved

ID:DIAN-D2431

Aim 1:Harmonize amyloid PET tracers

Aim 2:Harmonize tau PET tracers

Aim 3:Estimate the effect of multiple tracers in clinical trials

Title:APOE4 homozygous and autosomal dominant inheritance (PSENs/APP mutation) clinical characteristics and biomarker differences of Alzheimer's disease patients

Date of Request:09/08/2024

Status:pending approval

ID:DIAN-D2430

Aim 1:To explore whether there are differences in clinical characteristics and biomarkers between APOE4 homozygous and autosomal dominant (PSENs/APP mutation) patients with Alzheimer's disease who do not carry APOE4 genotype, further identify the interaction between APOE4 and Aβ changes, and guide the individualized diagnosis and treatment of clinical Alzheimer's disease patients.

Title:Evaluation of biomarkers changes associated with dominantly inherited Alzheimer’s disease to identify neurodegenerative and inflammatory biomarkers appropriate for Alzheimer’s clinical trials

Date of Request:09/05/2024

Status:approved

ID:DIAN-D2429

Aim 1:We hypothesize that findings from this cohort are likely to be informative for characterizing and monitoring sporadic forms of Alzheimer’s Disease as well.

Aim 2:We will focus on (1) the establishment of specific composite score to integrate several biomarkers to predict clinical outcomes sensitive to early disease and (2) the relationship of these biomarkers to markers of pathways of interest for future drug development (eg. anti-inflammatory pathways).

Title:How the skull and blood contribute immune cells to Alzheimer's disease (AD) pathology

Date of Request:09/03/2024

Status:approved

ID:DIAN-D2428

Aim 1:Analyze snRNAseq data from DIAN samples from the dataset published in Brase, et al. Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers. Nat Commun 14, 2314 (2023). https://doi.org/10.1038/s41467-023-37437-5 to compare against a mouse derived gene signature of brain engrafting immune cells.

Title:Establishing Noninvasive Biomarkers of Axonal Degeneration in Autosomal Dominant Alzheimer's Disease using Multishell Diffusion MRI

Date of Request:08/27/2024

Status:approved

ID:DIAN-D2427

Aim 1:The purpose of this study is to investigate axonal degeneration in Autosomal Dominant Alzheimer's Disease (ADAD) using advanced multishell diffusion magnetic resonance imaging (MRI) analyses, including Constrained Neurite Orientation Dispersion and Density Imaging (C-NODDI), to better understand the timing, location, and mechanisms of axonal degeneration in ADAD, and to identify potential biomarkers for AD progression and therapeutic efficacy.

Aim 2:To investigate axonal degeneration in ADAD using multishell diffusion MRI analyses, including C-NODDI, NODDI, and SMI.

Aim 3:To map axonal degeneration alterations as a function of years from symptom onset and integrate them within the temporal biomarker model of ADAD.

Aim 4To examine the relationship between axonal degeneration alterations and CSF- or blood/plasma-based biomarkers of AD pathology in ADAD.

Title:Hyperspectral retina imaging as a non-invasive marker to determine brain amyloid status

Date of Request:08/22/2024

Status:approved

ID:DIAN-D2426

Aim 1:1. The retinas of consenting volunteers from the DIAN cohort at site 952 will be non-invasively imaged using a hyperspectral retina camera and an optical coherence tomography (OCT) camera.

Aim 2:2. These retina images will be pooled into a larger training dataset to be analysed with an in-house developed machine learning program. This will be trained on the retina images against amyloid brain imaging scores (i.e. SUVR, Centiloid), to recognise high amyloid load based on the score cut offs. Other clinical data for these participants, such as APOE genotype, sex, age, amongst others, will be used as covariates in this training.