SUMMARY
The research laboratory led by Aivi T. Nguyen, M.D., studies the role of neuroimmune-mediated mechanisms in neurodegenerative diseases, particularly Alzheimer's disease and vascular dementia. As a board-certified neuropathologist, Dr. Nguyen integrates postmortem neuropathology with antemortem biomarkers such as neuroimaging, fluid markers and cognitive assessments to explore how microglial heterogeneity influences cognitive resilience and cerebrovascular dysfunction. Dr. Nguyen's research team specifically explores distinct microglial reactive subpopulations and investigates their protective roles in aging brains. The lab's research also examines perivascular macrophages and vascular-associated microglia at the blood-brain barrier, aiming to uncover mechanisms of white matter injury and vascular contributions to cognitive decline.
Dr. Nguyen performs diagnostic neuropathologic evaluations of brain tissue from participants in Mayo Clinic's Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging. These are longitudinal studies that integrate multimodal data to characterize aging over time.
Focus areas
- Microglial heterogeneity in Alzheimer's disease. Dr. Nguyen's research has uncovered a unique microglial subpopulation — amyloid-responsive microglia (ARM) — that appears to play a protective role in Alzheimer's disease. These cells are transcriptionally distinct and are reduced in individuals with high-risk genetic variants such as APOE ε4 and TREM2 R47H. Dr. Nguyen explores the relationship between ARM expression, amyloid and tau pathology, neuronal loss, and cognitive resilience, using both human brain tissue and transgenic mouse models.
- Cognitive resilience and neuroimmune response. Dr. Nguyen seeks to understand why some individuals maintain cognitive function despite significant Alzheimer's pathology. She studies people who are cognitively resilient or resistant using postmortem tissue and antemortem biomarkers to identify predictors of resilience. Her National Institutes of Health-funded K08 project uses structural modeling to link ARM expression with resilience, potentially offering tools to identify and support resilient aging in populations.
- Cerebrovascular disease and cognition. Dr. Nguyen's team examines neuropathologic scales of cerebrovascular disease and their predictive associations with cognition. The team also investigates underlying neuroimmune-driven mechanisms, such as how innate immune cells at the blood-brain barrier — particularly perivascular macrophages and vascular-associated microglia — contribute to cerebrovascular dysfunction and white matter damage. The team's work uses spatial transcriptomics and multiplex immunohistochemistry to characterize dysfunction of perivascular immune cells at the blood-brain barrier in aging brains, comparing these findings with MRI and cognitive data.
- Integration of biomarkers and pathology. Leveraging the Mayo Clinic Study of Aging, Dr. Nguyen correlates fluid biomarkers and neuroimaging with postmortem microglial expression. This integrative approach helps identify early predictors of neurodegeneration and cognitive decline, supporting the development of diagnostic and prognostic tools.
- Collaborative translational neuropathology. Dr. Nguyen collaborates across disciplines, contributing to studies on systemic inflammation, neuroimmunology and neurodegeneration. Her work integrates experimental neuropathology, digital image analysis, multi-omics analyses and machine learning to deepen understanding of glial activation and neuroimmune contributions to cognitive aging.
Significance to patient care
Dr. Nguyen studies why some people stay mentally sharp even when their brains show signs of Alzheimer's disease. She looks at how the brain's immune cells respond to damage, which could lead to new ways to protect memory and thinking. Her research may help healthcare professionals find early warning signs and create treatments that slow or prevent memory loss. She also studies how blood flow in the brain affects aging and dementia, which could lead to better care for people with blood vessel conditions.
Professional highlights
- American Association of Neuropathologists:
- Member, Education Committee, 2024-present.
- Neurodegenerative Disease Scholars Program Award, 2020-2023.
- Diagnostic Slide Session Award for Best Neurodegenerative Case, 2021.
- Honorable mention, Robert D. Terry Award, 2020.
- Member, Test Development and Advisory Committee, American Board of Pathology, 2024-present.
- Mentored Clinical Scientist Research Career Development Award (K08), National Institutes of Health, 2024-2029.