Lea Grinberg, M.D., Ph.D.

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SUMMARY

The research of Lea T. Grinberg M.D., Ph.D., focuses on the early mechanisms of neurodegenerative diseases, particularly Alzheimer's disease and frontotemporal lobar degeneration. Dr. Grinberg's work emphasizes the concept of selective neuronal vulnerability and the role of subcortical structures in early disease stages. By integrating classical neuropathology with cutting-edge techniques — such as high-resolution neuroimaging, iPSC-derived neuronal models and multi-omics — she aims to advance the understanding of disease progression, biomarker validation and neuropathological heterogeneity. Dr. Grinberg also addresses optimal health for everyone with dementia by studying diverse populations and has led international efforts to refine diagnostic criteria and identify novel disease entities.

Focus areas

• Early subcortical pathology in Alzheimer's disease. Dr. Grinberg's research has revealed that tau pathology first emerges in the dorsal raphe nucleus, preceding its spread to the cortex. This challenges the traditional view that neurofibrillary degeneration begins in the entorhinal cortex, highlighting the role of neuromodulatory systems in early symptoms such as depression and sleep disturbances. Her findings have significant implications for staging models and therapeutic strategies, particularly those targeting early subcortical changes.
• Neuropathological basis of sleep dysfunction. Dr. Grinberg leads investigations into how neurodegenerative diseases disrupt sleep-wake regulation. Her studies link specific subcortical neurons to sleep disturbances. They also show how sleep problems can affect diseases such as Alzheimer's and progressive supranuclear palsy.
• Validation of imaging and fluid biomarkers. Dr. Grinberg developed a platform that aligns high-resolution histology with neuroimaging data to validate biomarkers. This approach has been implemented at the Sao Paulo Autopsy Service, which houses the first 7T MRI in the southern hemisphere. Dr. Grinberg's platform supports clinical trials and collaborative studies aimed at improving diagnostic accuracy and early detection of neurodegenerative pathology.
• Ethnoracial diversity and neuropathological heterogeneity. Dr. Grinberg explores how genetic ancestry and socioeconomic factors shape patterns of neuropathology. Her research shows that individuals of African and Japanese descent may have different risk factors for Alzheimer's disease. By addressing how certain populations are understudied in dementia research, her work informs global health strategies.
• Selective neuronal vulnerability and disease heterogeneity. Dr. Grinberg's lab uses transcriptomics, proteomics and quantitative pathology to investigate why certain neurons are more susceptible to degeneration. Her work has identified brain cells called RORB-expressing excitatory neurons that are especially vulnerable in Alzheimer's disease. This discovery could help in finding new biomarkers and developing targeted treatments.

Significance to patient care

Dr. Grinberg studies how Alzheimer's disease and similar conditions begin and get worse, often before memory loss happens. By looking at early changes in the brain, especially in areas that control mood and sleep, she helps healthcare teams diagnose these diseases earlier and create better treatments. Her work also improves brain scans and lab tests to find these conditions sooner and more accurately. Dr. Grinberg includes people from many different backgrounds in her research so the results can benefit everyone. This ensures that all people with dementia get the best care and new treatments.

Professional highlights

• Member, Medical and Scientific Advisory Board, Alzheimer's Association, 2020-present.
• Member, Executive Committee, Global Brain Health Institute, 2018-present.
• Member, Executive Board, Biobank for Aging Studies, University of Sao Paulo Medical School, 2013-present.
• Funded by the National Institutes of Health:
  • Director, Human Validation Core, U54 Tau Center Without Walls, 2021-2026.
  • Chairperson, Brain Tissue Repository Oversight Committee, Framingham Heart Study, 2021-2025.
• University of California, San Francisco:
  • Co-leader, Neuropathology Core, Alzheimer's Disease Research Center, 2019-2025.
  • Co-leader, Neuropathology Core, Frontotemporal Dementia Program Project, 2017-2025.
  • Endowed professorship, John Douglas French Alzheimer's Foundation, 2020.
• Pioneer Award, Precision Medicine World Conference, 2023.
• American Association of Neuropathologists:
  • Hirano Award, 2022.
  • Honorable Mention, Weil Award, 2021.
• Chair, Neuromodulatory Subcortical Systems Professional Interest Area, International Society to Advance Alzheimer's Research and Treatment, 2020-2022.
• UNESCO/L'Oreal For Women in Science Award, L'Oreal Foundation, United Nations Educational, Scientific and Cultural Organization, 2009.