DIAN Data Resource Requests

Title:Longitudinal tau PET in dominantly inherited Alzheimer’s disease

Date of Request:07/04/2019

Aim 1:a) to understand the role tau PET imaging can play as a marker of early Alzheimer’s disease for clinical diagnostic purposes and also as a biomarker in trials of individuals with autosomal dominantly inherited forms of Alzheimer’s disease (ADAD)

Aim 2:b) to optimize static and dynamic methods of tau PET analysis in order to achieve better longitudinal consistency and reduce sources of within-subject variability

Aim 3:c) to improve understanding of when and where tau deposition occurs, and how these relationships change over time;

Aim 4d) to determine the relationship between changes in tau deposition and changes related to neurodegeneration and cognitive decline; and

Title:Comparing CSF biomarkers of AD in Down Syndrome and autosomal dominant AD

Date of Request:06/21/2019

Aim 1:To analyze and compare levels of established and novel CSF biomarkers (Aβ40, Aβ42, tTau, pTau, VILIP-1, Ng, SNAP-25, YKL-40, NfL, and sTREM2) between ABC-DS and DIAN cohorts.

Title:Comparison between Dominant Inherit Alzheimer Disease and sporadic early-onset Alzheimer’s disease.

Date of Request:06/03/2019

Aim 1:To compare clinical presentation, neuropsychological performance and cognitive decline rate between DIAD and sporadic EOAD.

Aim 2:To examine the regional distribution of tau, amyloid-β, glucose metabolism, and structural atrophy in DIAD and sEOAD.

Aim 3:To determine CSF biomarkers levels and biomarkers rate of change in DIAD and sEOAD.

Title:Development of a robust quantitative systems pharmacology model of amyloid beta and tau pathways for clinical trial design and decision making in Alzheimer’s disease and dementia

Date of Request:05/24/2019

Aim 1:Calibrate the QSP model to longitudinal biomarker changes for different mutation status

Aim 2:Virtual patient creation to capture the patient variability

Aim 3:Predict drug treatment effect with virtual patient population

Title:Isogenic APOE isoform glia response to amyloid in brain organoids

Date of Request:05/16/2019

Aim 1:Generation of induced pluripotent stem cells from APP (and/or PS1) mutations

Aim 2:Differentiation of the iPSC to organoids to generate beta-amyloid aggregates and differentiation of isogenic APOE iPSC to microglia

Aim 3:Co-culture isogenic APOE 33 and APOE 44 microglia with the organoids from APP (and/or PS1) mutations

Aim 4Single cell transcriptomic analysis from co-cultured organoids

Title:Protective Factors in DIAN

Date of Request:05/15/2019

Aim 1:Analyze the rates of change in cognition and AD biomarkers in ADAD mutation carriers that are past expected age of onset and are not showing any symptoms

Title:Alterations of the Brain Connectome in Familial Alzheimer's disease

Date of Request:05/14/2019

Aim 1:To define the changes in the structural and functional connectomes in symptomatic and asymptomatic mutation carriers with ADAD

Aim 2:To map these changes as a function of estimated years to onset of AD

Aim 3:To assess whether the connectome alterations are associated with cerebrospinal fluid and blood biomarkers, voxel-wise amyloid, tau and glucose metabolism PET, and clinical measures

Title:Alterations of the Brain Connectome in Familial Alzheimer's disease

Date of Request:05/14/2019

Aim 1:To define the changes in the structural and functional connectomes in symptomatic and asymptomatic mutation carriers with ADAD

Aim 2:To map these changes as a function of estimated years to onset of AD

Aim 3:To assess whether the connectome alterations are associated with cerebrospinal fluid and blood biomarkers, voxel-wise amyloid, tau and glucose metabolism PET, and clinical measures

Title:Cognitive markers of preclinical Alzheimer's disease through psycholinguistic semantic measures

Date of Request:05/03/2019

Aim 1:To estimate the temporality of semantic impairment in the preclinical phase of Alzheimer’s disease

Title:Sequencing cognitive decline within familial AD progression

Date of Request:04/09/2019

Status:Pending

ID:DIAN-D1909

Aim 1:Construct an event-based model of cognitive decline in dominantly-inherited AD from DIAN data using a similar set of outcomes to those in [Baker–AlzDem:DADM-2017]. This will include separating subscores into cognitive domains which will allow us to validate the new technique against current thinking in neurology and neuropsychology.

Aim 2:Compare different versions of the event-based model to determine which limitations are important to address, which elements of the model are essential, which variants of the model (and its parameters/settings) are feasible, and how much complexity can be supported by different-sized data sets.

Aim 3:Extend the model to include a broader set of biomarker data including tau PET, amyloid PET, CSF (molecular changes), MRI, DTI (atrophy and microstructural changes) and other factors. This will enable cognitive decline to be positioned within the pathophysiological cascade.