The National Institute on Aging awarded a $480,536 Project Grant under the Aging Research program (CFDA 93.866) to The Jackson Laboratory to fund research aimed at improving treatment for Alzheimer's disease and related dementias (ADRD). The project will assess whether manipulating the angiopoietin/tie2 (ANG/TIE2) signaling pathway can preserve blood-brain barrier (BBB) integrity and prevent cerebrovascular dysfunction, which are major contributors to many ADRDs. The research approach involves both genetic and pharmacological targeting of the ANG/TIE2 pathway in a mouse model of ADRD. The Jackson Laboratory will lead the overall project, including conducting in vivo and ex vivo studies to evaluate cognition, cerebrovascular function, amyloid deposition, neurodegeneration, and neuroinflammation. The Trustees of Indiana University will serve as a sub-grantee, providing specialized expertise in in vivo imaging and pharmacokinetic/pharmacodynamic modeling. The project is expected to run from Sep 1, 2023 to Aug 31, 2025.