Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
PROJECT ABSTRACT Alzheimer’s disease (AD) is marked by progressive cognitive decline and blood-brain barrier (BBB) breakdown, especially in individuals carrying the high-risk APOEε4 genotype. Yet, some APOEε4 homozygotes remain cognitively intact, suggesting the presence of genetic resilience mechanisms. Through whole-genome sequencing of resilient APOEε4 carriers, we identified a rare protective missense variant in LAMA1 (G967D), a key laminin subunit critical for BBB integrity. We hypothesize that this LAMA1 variant modifies extracellular matrix (ECM) composition, mitigating BBB dysfunction. In Aim 1, we will generate the LAMA1 variant in human iPSC- derived astrocyte-endothelial co-cultures within 3D hydrogels and assess ECM remodeling and proteomic changes. In Aim 2, we will use CRISPR-edited APOEε4 zebrafish models to examine the in vivo impact of orthologous LAMA1 genetic variant on BBB dysfunction, vessel leakage, gliosis, and gene expression in BBB cell types. By integrating human and zebrafish models with imaging, single-cell transcriptomics, and proteomics, this project will provide novel mechanistic understanding of LAMA1 genetic variant and its therapeutic potential for maintaining BBB homeostasis in genetically at-risk populations.
Grant Summary
Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $452K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $452K
2028-05-31
- 1Confirm your organization is eligible for Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease from NINDS - National Institute of Neurological Disorders and Stroke, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
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Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease: Frequently Asked Questions
Who is eligible for the Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease?
Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease is offered by NINDS - National Institute of Neurological Disorders and Stroke and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease provide?
Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease provides up to $452K per award from NINDS - National Institute of Neurological Disorders and Stroke. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease deadline?
Applications for Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease?
To apply for Dissecting the role of LAMA1 genetic variant in modulating blood-brain barrier integrity and protection against APOE4-driven Alzheimer's disease, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NINDS - National Institute of Neurological Disorders and Stroke.