Search DIAN Tissue Requests
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. DIAN-T1004), the full request has been submitted and is either approved, disapproved or in process.
Sto mostrando 21 - 30 di 79
Houlden and Kullmann/Houlden
Dominant and Recessive Intronic Repeat Expansions in Neurodegeneration
Screen for the GGC repeat expansion in the NOTCH2NLC gene recently associated with dominant or sporadic neurodegeneration from our and Japanese labs.
Screen the AAGGG recessive expansion seen in the RF gene associated with ataxia, MSA-like phenotype and neurodegeneration.
We will haplotype patients with expansions to understand relationships between samples, SNPs associated with the disease and possible founder effects.
Feedback results to be paired with biobank samples
RIPK1 regulated metabolic biomarkers
Compare the baseline distribution of RIPK1 regulated metabolic biomarkers in CSF samples from DIAN patients vs. cognitively normal non-carrier family member controls
Generate biomarker hypothesis to inform the decision making for a DIAN population in phase2a clinical trial with RIPK1 inhibitors
Steven M. Greenberg
CSF Biomarkers for Dutch-type Hereditary Cerebral Amyloid Angiopathy
1. Perform multiplex immunoassay measurements of a range of candidate biomarkers in cerebrospinal fluid (CSF) samples from carriers and non-carriers of the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation enrolled in DIAN.
2. Perform parallel immunoassays on plasma samples drawn at similar timepoints to determine the correlation between CSF and plasma concentrations.
3. Correlate CSF and plasma biomarkers with neuroimaging, biochemical and clinical features in the enrolled mutation carriers.
Immune Cell Pathways in ADAD
No Request Made
To identify innate immune cell phenotypes and gene regulatory networks in familial AD. Innate immune genes and loci harboring immune genes have been associated with sporadic AD though less is known about cell type specific immune gene networks in familial AD. Evidence from studies including those from DIAN investigators have demonstrated early changes in microglial proteins, in mutation carriers prior to clinical onset of disease. This suggests that microglial or innate immune cell activity, be it loss of homeostatic function, activation of inflammatory or tissue repair responses, disease associated responses or other yet to be defined phenotypes may contribute to FAD progression and serve as a potential therapeutic target in combination with other therapies. While modulating immune pathways in FAD may be a viable intervention, a clearer understanding of the disease relevant drivers of neural and peripheral immune pathways are needed for appropriate targeting. We propose to evaluate transcriptomic data from single nuclei and microglial enriched nuclei, isolated from frozen cortical tissue (parietal or frontal – depending upon tissue availability) from 20 FAD carriers and establish gene expression modules annotated by neural cell type. These data will be analyzed in comparison to 20 sporadic AD and 10 pathology negative controls (funding pending for sporadic AD cases). Further computational approaches by collaborators at SAGE Bionetworks will be pursued to identify proximal molecular networks in microglial, neuronal, and other glial cell types that are both shared and distinct between FAD and SAD. Additionally, we will determine the relative representation of immune cell populations and diversity of phenotypes. These studies aim to highlight the networks mediating glial biology associated with FAD. In addition, identification of the molecular programs which are shared or distinct between FAD and SAD will be relevant for therapeutic design and disease modeling for both forms of disease.
The Role of TRIC chaperonin in AD pathogenesis
To test the hypothesis that TRIC chaperonin repression occurs in neuronal differentiated AD IPSC compared to WT IPSC.
To test the hypothesis that autophagy dysfunction occurs in neuronal differentiated AD IPSC compared to WT IPSC.
To test the hypothesis that manipulation of the TRIC chaperonin can alter autophagy function of neuronal differentiated AD IPSC.
To test the hypothesis that manipulation of the TRIC chaperonin alters AB levels in neuronal differentiated AD IPSC.
Erik Johnson, Allan Levey
A Proteomic Network Comparison of Autosomal Dominant and Sporadic Alzheimer’s Disease
Compare the brain protein network alterations that characterize autosomal dominant AD with those observed in sporadic early-onset AD
Mitochondrial deficits in AD patient iPSC-derived neurons
Investigate abnormalities in mitochondrial dynamics and quality control in patient iPSC-derived human neurons
Investigate molecular mechanism underlying mitochondrial dynamic and quality control abnormalities in patient iPSC-derived human neurons
Mechanistic and functional assessment of sporadic early-onset AD
Investigate amyloid-related mechanisms of familial and sporadic EOAD patient-derived fibroblasts, patient iPSC-derived neurons and directly converted neurons
Assess the function, structure and potential pathological pathways of sporadic EOAD, familial EOAD, healthy and LOAD patient-derived iPSC-derived neurons and directly converted neurons
Dr. Tammie Benzinger
Imaging Tauopathy in the Dominantly Inherited Alzheimer Network (DIAN)
Aim 1: To study the temporal dynamics of tau deposition (using AV-1451). This proposal studies tauopathy in relation to existing biomarkers within DIAN participants including: CSF (CSF tau, p-tau, Aβ42), neuroimaging [Aβ PET and structural and functional magnetic resonance imaging (MRI)], and cognitive performance [clinical dementia rating sum of boxes (CDR-SB) and neuropsychometric testing]. We will relate AV1451 uptake to EYO to determine timing of tau changes relative to conversion to symptomatic AD. Hypothesis: PET tau changes occur after Aβ (CSF Aβ42 and PET Aβ) and after soluble CSF tau but before MRI (structural or functional) or neuropsychometric changes in DIAN.
Aim 2: To study the spatial (both local and distributed) changes of tau deposition (using AV-1451). We will examine the spread of tauopathy along structural and functional connections. We will identify the spatial pattern of tauopathy during the crucial transition from preclinical to symptomatic AD. Additionally, using novel mathematical models, we will correlate the topography of tau PET with both cross-sectional and longitudinal spatial patterns seen with other imaging biomarkers (Aβ PET and MRI [structural and functional]). Hypothesis: Phenoconversion from cognitively normal to symptomatic dementia is associated with neocortical tau deposition. The spread of tau deposition is predicted by functional/structural connections.
Aim 3 (exploratory): Study the relationship between in vivo tau deposition and neuropathology. We will perform quantitative measures of cortical tauopathy NFT, NP, and neuropil thread (NT) burden in twenty-five brain areas using tau-immunostained sections and automated stereological methods. We will perform quantitative autoradiography with [3H]AV-1451 in the same tissue samples to validate receptor binding specificity and quantify tauopathy. Neuropathological results will be aligned with in vivo imaging using an ex vivo MRI prior to sectioning. Hypothesis: There will be a strong correlation between tau burden as assessed by AV-1451 in vivo imaging, [3H]AV-1451 autoradiography, and anti-tau antibodies.
Development of blood-based proteomic biomarkers of Alzheimer's disease
Our study aims to identify a blood-based biomarker panel using SWATH-MS that can detect AD at an early asymptomatic stage