Data Release 25.3 includes updates to human studies including the Living Brain Project and several new model studies from the Mayo Clinic.
Human
The WHICAP_Immunoprofiling Study
This study generates cytometric data and bulk RNAseq profiles of peripheral blood mononuclear cells (PBMC) from older individuals.
- This release provides flow cytometry data for peripheral blood mononuclear cells sourced from 319 individuals, as well as clinical metadata for all individuals and biospecimens.
The LBP Study
This study provides bulk RNAseq data from prefrontal cortex samples from a living brain cohort matched for age and sex to a postmortem brain cohort. The living samples were collected from individuals undergoing a deep brain stimulation electrode implantation surgery.
- This release provides single-cell RNA sequencing and Whole Genome Sequencing fastq files sourced from 31 individuals. It also provides updated assay and clinical metadata.
The AMP-AD_DiverseCohorts Study
The AMP-AD Diverse Cohorts Study is a cross-consortium project generating harmonized datasets from diverse human cohorts. This study provides post-mortem multi-omic data from over 850 individuals, including 305 Black or African American individuals and 336 Hispanic or Latino individuals representing the spectrum of Alzheimer’s Disease phenotypes. Data is generated from research teams at Rush University, Emory University, the Mayo Clinic, Columbia University, and Mt Sinai Medical School.
- This release provides additional harmonized neuropathology data for 765 Diverse Cohorts study participants.
Models
The ISB_Taner_CollagenDomain Study
This study explores the utility of a 126-amino acid collagen domain (CD) derived from the C1qTNF3 protein as a fusion partner to chaperone secreted proteins, extracellular “decoy receptor” domains, and single-chain variable fragments (scFvs). It also tests the effect of overexpression of secreted CD by itself influenced cognitive function or amyloid pathology and RNA expression, delivering rAAV2/1-CD into the cerebral ventricles of newborn TgCRND8 mice to find that there is no effect on cognitive function, amyloid plaque burden or RNA expression changes.
- This release provides gene expression files sourced from 12 individual mice, RNA sequencing assay metadata, and clinical metadata.
Prior studies from this lab have demonstrated the effects of intracerebral overexpression of pro- and anti-inflammatory cytokines on amyloid beta burden in TgCRND8 mice, a preclinical model of AD-type amyloidosis. This study overexpresses Cxcl10 and examines the effects on the RNA transcriptome.
- This release provides gene expression files sourced from 6 individual mice, RNA sequencing assay metadata, and clinical metadata.
M42 proteins, identified by mass spectroscopy, appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD. We find that overexpression of midkine (MDK) or pleiotrophin (PTN) via AAV transgenesis into neonatal TgCRND8 mice leads to accelerated accumulation of Abeta in plaques and CAA.
- This release provides gene expression files sourced from 24 individual mice, RNA sequencing assay metadata, and clinical metadata.
The ISB_Taner_sIL10r_sIL4r Study
This study hypothesizes that a decoy receptor strategy specifically targeting Il10 and Il4 signaling could have a disease-modifying effect. To test this hypothesis, this study derivatizes the ectodomains of mouse Il10R (sIl10R) and mouse Il4R (sIl4R) into corresponding recombinant solubilized receptor forms and delivered these intracranially into neonatal TgCRND8 mice. These data reveal that decoy receptor mediated targeting of physiological Il10 or Il4 signaling can beneficially impact amyloid deposition and thus represent novel immunomodulatory approaches for AD therapy.
- This release provides gene expression files sourced from 32 individual mice, RNA sequencing assay metadata, and clinical metadata.
Prior studies from this lab have demonstrated the effects of intracerebral overexpression of pro- and anti-inflammatory cytokines on amyloid beta burden in TgCRND8 mice, a preclinical model of AD-type amyloidosis. This study overexpresses TGFbeta and examines the effects on the RNA transcriptome.
- This release provides gene expression files sourced from 32 individual mice, RNA sequencing assay metadata, and clinical metadata.