This federal Project Grant award from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310) provides $2,357,335 to study neuronal dysfunction in Down syndrome (DS) and its link to Alzheimer's disease (AD). The key products and services delivered under this award include: Utilizing induced pluripotent stem cell (iPSC)-derived cortical organoids and assembloids to examine the cellular, transcriptomic, and motility-related...
The University of California, San Diego (UCSD) was awarded a $1,698,323 Project Grant from the National Institute on Aging (CFDA 93.866 Aging Research) to develop and validate a mouse model for Alzheimer's disease in Down syndrome (DS-AD). The goal is to create a genetically modified mouse that replicates key pathological features of DS-AD, including amyloid plaques, congophilic angiopathy, and neurofibrillary tangles. In the initial R61 phase, the researchers will demonstrate feasibility,...
The National Institutes of Health Trans-NIH Research Support program awarded a $4,010,262 Project Grant to the University of Illinois to study the role of amyloid precursor protein in neurogenesis and Alzheimer's disease pathology in Down syndrome. The three-year grant will support research examining how overexpression of amyloid precursor protein, which is located on chromosome 21 and thus triplicated in Down syndrome, impacts neural stem cell proliferation, neuronal differentiation, and...
This Project Grant award, totaling $780,000.00, was provided by the National Institute on Aging (NIA) under the Aging Research federal grant program (CFDA 93.866). The award aims to elucidate the epigenetic mechanisms responsible for allelic inactivation of protein-coding genes within the Down Syndrome Critical Region and the Alzheimer's Disease-associated APP gene on Chromosome 21. The research will utilize human and mouse cell-based assays to investigate the molecular and cellular mechanisms...
This $3,845,311 Project Grant was awarded by the National Institute on Aging (NIA) under the Aging Research program (CFDA 93.866) to the University of California, San Diego (UCSD). The award aims to use induced neurons (iNs) derived from mild cognitive impairment (MCI) patients to investigate the early determinants and pathogenesis of Alzheimer's disease (AD). The project will integrate polygenic risk scores for AD with multi-omic profiling of MCI patient-derived iNs to better understand the...
This Project Grant award from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310) provides $322,000.00 to Case Western Reserve University to perform the following: Analyze electroencephalographic (EEG) and plasma Alzheimer's disease (AD) biomarker data collected during a previous clinical trial studying the effects of the drug memantine on adolescents and young adults with Down syndrome. The analysis will examine the...
This Project Grant award of $429,000 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research to understand the cellular and synaptic mechanisms underlying cognitive disabilities in Down syndrome. The award to the University of Colorado-Denver will utilize a novel combination of two-photon microscopy, electrophysiology, chemogenetics, and pharmacological...
This federal Project Grant award, worth $2,010,230, was provided by the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865). The award will fund research at the University of California, San Diego (UCSD) to comprehensively investigate the intricate nuclear-metabolic interplay in Down syndrome (DS). The multifaceted study aims to characterize and modulate the nuclear-metabolic axis at three...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 Aging Research) to The Trustees of Columbia University in the City of New York provides $452,375 to investigate the potential use of the APLP1 protein as an early biomarker for Alzheimer's disease in individuals with Down syndrome. The project aims to leverage recent findings linking endosomal trafficking defects to the early pathology of Alzheimer's disease, which is observed decades before classical...
This $3.44 million project grant from the Department of Health and Human Services National Institutes of Health Office of the Director, under the Trans-NIH Research Support program (CFDA 93.310), will fund research at the University of Massachusetts Medical School to suppress aneuploidy-associated phenotypes in Down syndrome. Specifically, the researchers will identify the mechanisms by which an extra copy of chromosome 21 affects nuclear structure and function in cells, investigate how...
This Project Grant award from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310) provides $3,317,325.00 to the University of California, Irvine to investigate the role of immune deregulation and nerve growth factor (NGF) dysfunction in the development of Alzheimer's disease (AD) in individuals with Down syndrome (DS). The key products and services to be delivered under this 5-year grant include:
Utilizing a multi-pronged approach combining unbiased discovery techniques (transcriptomics and proteomics) and targeted biomarker analyses across complementary model systems (DS brain tissue, human trisomy 21 cortical cultures) to elucidate the relationships between immune dysregulation, NGF metabolic dysfunction, and AD-related neurodegenerative changes in DS. This work will involve sub-awards to the New York University School of Medicine for specialized tissue sample analysis and biomarker assessments. The comprehensive research aims to establish the temporal ordering of immune and trophic factor alterations in the context of the AT(N) framework within a longitudinal DS cohort, with the goal of informing future preventive trials and identifying novel AD biomarkers and therapeutic targets for this vulnerable population.