Federal Project Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded $452,375 to The Trustees of Columbia University in the City of New York (Health Sciences Division) on June 15, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The project, which will conclude May 31, 2028, focuses on investigating the protective role of a rare LAMA1 genetic variant (G967D) in maintaining blood-brain barrier (BBB) integrity and conferring resilience against Alzheimer's disease in APOEE4 carriers. Research activities include generating the LAMA1 variant in human induced pluripotent stem cell (iPSC)-derived astrocyte-endothelial co-cultures within three-dimensional hydrogels to assess extracellular matrix remodeling and proteomic changes, and utilizing CRISPR-edited APOEE4 zebrafish models to examine the in vivo impact of the orthologous LAMA1 genetic variant on BBB dysfunction, vessel leakage, gliosis, and gene expression patterns.

The research deliverables will integrate human cell culture models and zebrafish in vivo systems with advanced analytical methodologies including imaging, single-cell transcriptomics, and proteomics to elucidate mechanistic understanding of how the LAMA1 genetic variant modulates BBB homeostasis in genetically at-risk populations. These findings are intended to establish the therapeutic potential of the identified genetic variant and inform strategies for maintaining BBB integrity in individuals carrying the high-risk APOEE4 genotype.