Announcing The Carol and Gene Ludwig Center for Research on Neurodegeneration 2025 Pilot Grant Awardees

July 17, 2025

The Carol and Gene Ludwig Center for Research on Neurodegeneration is pleased to announce the 2025 recipients of its Pilot Grant Program in Neurodegeneration, which supports high-risk, high-reward research aimed at advancing understanding of Alzheimer’s disease (AD) and other neurodegenerative diseases. This year’s grants were awarded to two compelling studies that investigate how vascular disease, inflammation, different cerebrovascular pathologies, and blood-brain barrier dysfunction, relate to the progression of AD. 

2025 Pilot Grant Awardees

Pictured left to right: Andrew Teich, MD, PhD, and Lawrence Honig, MD, PhD

The first project led by Drs. Andrew Teich and Lawrence Honig, is entitled “A Proposal to study the Molecular and Cellular basis of Alzheimer’s Disease-associated Microbleeds, Microinfarcts, and Associated Vascular disease”. The goal of this project is to characterize the molecular and cellular nature of microbleeds and microinfarcts that are associated with AD. The Teich-Honig team note the importance of microbleeds and microinfarcts in AD pathology and treatment and that how, these vascular diseases relate to AD is not well understood. The research will focus on pathology, using also brain MRI scans as guidance, and examine how these microbleeds and microinfarcts are connected to a condition called cerebral amyloid angiopathy (CAA). Microbleeds are both risk factors for side effects, and side effects themselves, in new monoclonal antibody Alzheimer’s treatments. Some of the side effects to anti-amyloid treatment include brain swelling (ARIA-E) or brain bleeding (ARIA-H). 

One of the major questions will expand on vascular disease and AD pathology to use Machine Learning to identify morphologic features that associate with AD microinfarcts, microbleeds, and associated vascular disease. The secondary approach will use histochemical and immunohistochemical studies and laser capture transcriptomics to characterize microhemorrhages and microinfarcts and identify gene expression changes close in proximity and at a distance from the AD vascular changes. 

By answering these questions, the project hopes to shed light on how vascular damage contributes to Alzheimer’s and to help improve how AD is diagnosed and treated in the future. 

2025 Pilot Grant Awardees - 2

Pictured left to right: Clarissa Waites, PhD, and Ulrich Hengst, PhD.

The second project, “The role of IFN1 signaling in chronic stress-induced disruption of the blood-brain barrier” is led by Drs. Clarissa Waites and Ulrich Hengst. The significance of this study is that chronic stress is a major health and AD/ADRD risk factor. Inflammation and cerebrovascular pathology are a major target in AD/ADRD, and this proposal aims to identify avenues for novel therapeutic approaches through tackling the mechanistic understanding of how AD-linked vascular changes occur and how they are precipitated and/or accelerated by the AD risk factor - stress. 

The hypothesis is that chronic activation of type interferon 1 (IFN1) signaling, triggered by stress-induced glucocorticoid (GC) elevation, drives cerebrovascular pathology through immune-mediated mechanisms. Using conditional knockout mouse models, the investigators propose to dissect the distinct contributions of IFN1 signaling in myeloid cells and brain endothelial cells to GC stress-induced blood brain barrier (BBB) breakdown, inflammation, and immune cell infiltration. 

The team’s use of innovative in vivo approaches drives the translational potential and implications for understanding and potentially mitigating GC-related BBB dysfunction in mild cognitive impairment and AD. 

Both projects reflect the Ludwig Center Pilot Program’s commitment to advancing innovative, high-impact research in neurodegeneration. By fostering collaboration among diverse research teams, the program supports translational efforts that bridge basic science and clinical application, ultimately accelerating the development of therapeutic strategies that have the potential to transform Alzheimer’s disease. For more information on the awarded projects or the Pilot Grant Program, please contact Nadia Propp, np2221@cumc.columbia.edu.