Search DIAN Data Resource Requests

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:pending approval

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:pending approval

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:pending approval

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.

Title:Social Determinants of Health in Autosomal Dominant Alzheimer's Disease in LatAm

Date of Request:08/22/2024

Status:pending approval

ID:DIAN-D2425

Aim 1:To analyze the impact of SDoH on symptom onset in ADAD in LatAm

Title:Establishing the utility and sensitivity of high-frequency cognitive assessments in Dominantly Inherited Alzheimer Disease.

Date of Request:08/22/2024

Status:pending approval

ID:DIAN-D2424

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

Title:Knowledge-enhanced Cognitive System for Alzheimer’s Disease

Date of Request:07/28/2024

Status:pending approval

ID:DIAN-D2423

Aim 1:Construct an AD-KG by utilizing multiple curated resources, literature, and individual data across different domains and studies for AD.

Aim 2:Construct OKG for harmonization, imputation, and knowledge representation of AD-related multi-omics data.

Aim 3:Construct NKG for presentation, imputation, and knowledge representation of neuroimaging data and NOKG for knowledge representation of neuroimaging omics association maps, including, building a functional-facilitated structural connectome (FFSC) atlas, training cognitive systems methods for imputation and synthesis, constructing NKG and NOKG, respectively, to augment and complement AD-KG in 1).

Aim 4Develop an AD-KG-enhanced cognitive system (AD-KG-CS) for clinically transformative research.

Title:Association between white matter (WM) specific tracts integrity and cognition profile in asymptomatic and symptomatic individuals whit Autosomal Dominant Alzheimer's Disease.

Date of Request:07/27/2024

Status:pending approval

ID:DIAN-D2422

Aim 1:Identify patterns of cognitive profile in asymptomatic and symptomatic individuals with Autosomal Dominant Alzheimer's Disease.

Aim 2:Assess microstructural integrity of WM specific tracts in asymptomatic and symptomatic individuals with Autosomal Dominant Alzheimer's Disease.

Aim 3:Explore the relationship between cognitive profile and changes in WM specifict tracts on potential shared mechanisms and differences in asymptomatic and symptomatic individuals with Autosomal Dominant Alzheimer's Disease.

Title:Dominantly inherited Alzheimer's disease and Dutch-type cerebral amyloid angiopathy: a comparison of fluid biomarkers, imaging, cognitive and neuropsychiatric measures

Date of Request:07/24/2024

Status:pending approval

ID:DIAN-D2421

Aim 1:To examine the difference between D-CAA and ADAD in CSF and blood biomarkers, including Amyloid beta (Aβ) 40, Aβ42, total tau, p-tau181, matrix metalloproteinase 9 (MMP-9), fibrinogen, vascular cell adhesion molecule-1 (VCAM-1), Neurofilament light chain (NfL), and Glial Fibrillary Acidic Protein M(GFAP), over time.

Aim 2:To identify changes over time in cognitive domains, such as executive functions and memory, and NPS like depression, anxiety, and apathy in (pre)clinical stages of ADAD and D-CAA

Aim 3:To examine the relationship between fluid and imaging (amyloid PET and MRI) biomarkers in ADAD and D-CAA, and their relationship with cognition and NPS in (pre)symptomatic ADAD and D-CAA.

Aim 4To investigate whether demographic and lifestyle factors (such as age, education, exercise and socioeconomic status) influence on cognitive decline and NPS in (pre)symptomatic ADAD and D-CAA over time and whether these changes affect functioning and caregiver burden.

Title:Analysis of proteomic signatures of MFG-E8 and medin amyloid in patients with autosomal dominant Alzheimer’s disease (ADAD)

Date of Request:07/21/2024

Status:approved

ID:DIAN-D2420

Aim 1:To test the association between MFG-E8 levels and neuroimaging markers of CAA

Aim 2:To test modulating factors of biofluid MFG-E8 levels including APOE e4 genotype and vascular risk factors

Aim 3:To determine the proteomic network and levels of medin associated with alterations in MFG-E8