Our Mission
Neuroimmunology is the most rapidly advancing field of research in the study of brain diseases and particularly in Alzheimer’s disease. We are studying how immune cells interact with the brain during Aging, in Alzheimer’s disease and in individuals with Down syndrome. We also study the mechanistic link between pregnancy with a Down syndrome fetus and the elevated risk of maternal cognitive decline.
How Pregnancies Cause Maternal Alzheimer’s Risk
In this project, we study a uniquely troubling medical complication: mothers carrying a Down syndrome fetus, caused by a trisomy in chromosome 21, face a significantly elevated risk of late-onset Alzheimer’s disease later in life.
We are pursuing a first-of-its-kind mechanistic exploration of feto-maternal molecular transfer during pregnancy to test whether Alzheimer’s disease-related toxic proteins can cross into the maternal brain and seed amyloid deposition. Combining genomic, proteomic, transcriptomic, and behavioral analyses, we aim both to reveal the biological pathways that drive this maternal risk and to identify preventative strategies that block harmful fetal-to-maternal influences on cognition.
These studies are at the nexus of neuroimmunology, developmental biology, neurodegeneration, and translational neuroscience, with potential impact on preventative care for families affected by the Trisomy of chromosome 21.
Meningeal Immunity in Alzheimer’s Disease and Aging
We are uncovering a novel immunological frontier in Alzheimer’s disease and brain aging by studying how adaptive immune B cells organize into unique structures termed Ectopic lymphoid structures (ELS) at the brain’s protective boundaries, namely, the brain meninges.
These ectopic immune hubs have only recently been implicated in chronic brain pathology, and our work shows that meningeal B cells may actively drive or modulate Alzheimer’s progression and inflammaging. Using advanced immunofluorescence, high-dimensional flow cytometry, RNA sequencing and light-sheet microscopy, we map ELS formation across Alzheimer’s mouse models and aging mice to identify the B cell subpopulations that shape neuroimmune interactions at the brain surface.
Our goal is to redefine how immune architecture influences neural health and to identify immune-based targets for early intervention in age-related cognitive decline.
Immune Dysregulation and Cognition in Down Syndrome
Down syndrome presents a striking blend of immune dysregulation, Alzheimer’s disease-related cognitive decline and vulnerability to infections, that predisposes individuals to early-onset Alzheimer’s.
Individuals with trisomy 21 have both immune system abnormalities and lifelong overexpression of the amyloid precursor protein (APP), a key driver of amyloid-β accumulation, a hallmark of Alzheimer’s disease.
We investigate how distinct B cell subsets contribute to amyloid-related pathology and cognitive decline in DS using cutting-edge flow cytometry, histopathology and advanced microscopy, in translational Down syndrome mouse models. By dissecting these links, our research seeks mechanistic insights that could slow or prevent cognitive decline in individuals with Down syndrome, and potentially broader Alzheimer’s populations.