Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium

Wassim Elyaman; Lawrence J Stern; Ning Jiang; Dallin Dressman; Philip Bradley; David Klatzmann; Elizabeth M Bradshaw; Donna L Farber; Sally C Kent; Shahab Chizari; Kristen Funk; Davangere Devanand; Kiran T Thakur; Towfique Raj; Osama Al Dalahmah; Rani A Sarkis; Howard L Weiner; Neil A Shneider; Serge Przedborski

doi:10.1002/alz.14548

Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium

Alzheimers Dement. 2025 Jan 27:e14548. doi: 10.1002/alz.14548. Online ahead of print.

Authors

Wassim Elyaman^{1

2

3

4}, Lawrence J Stern⁵, Ning Jiang⁶, Dallin Dressman^{1

2

3

4}, Philip Bradley⁷, David Klatzmann⁸, Elizabeth M Bradshaw^{1

2

3

4

9}, Donna L Farber¹⁰, Sally C Kent¹¹, Shahab Chizari⁶, Kristen Funk¹², Davangere Devanand¹³, Kiran T Thakur⁴, Towfique Raj¹⁴, Osama Al Dalahmah¹⁵, Rani A Sarkis¹⁶, Howard L Weiner¹⁷, Neil A Shneider^{3

4

18}, Serge Przedborski^{3

4}

Affiliations

¹ Division of Translational Neurobiology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
² The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
³ Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, New York, USA.
⁴ Department of Neurology, Columbia University Medical Center, New York, New York, USA.
⁵ Department of Pathology, and Immunology and Microbiology Program, UMass Chan Medical School, Worcester, Massachusetts, USA.
⁶ Department of Bioengineering, Institute for Immunology and Immune Health, Center for Cellular Immunotherapies, Abramson Cancer Center, Institute for RNA Innovation, Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
⁸ INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France.
⁹ Carol and Gene Ludwig Center for Research on Neurodegeneration, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
¹⁰ Department of Microbiology and Immunology, and Department of Surgery, Columbia University, New York, New York, USA.
¹¹ Diabetes Center of Excellence, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
¹² Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina, USA.
¹³ Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.
¹⁴ Department of Genetics and Genomic Sciences & Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁵ Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, New York, USA.
¹⁶ Epilepsy Division, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁷ Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁸ Eleanor and Lou Gehrig ALS Center, Columbia University, New York, New York, USA.

PMID: 39868844
DOI: 10.1002/alz.14548

Abstract

This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases. HIGHLIGHTS: Researchers gathered to discuss approaches to study T cells in brain disorders. New technologies allow high-throughput screening of antigen-specific T cells. Microbial infections can precede several serious and chronic neurological diseases. Central and peripheral T cell responses shape neurological disease pathology. Immunotherapy can induce regulatory T cell responses in neuroinflammatory disorders.

Keywords: Alzheimer's disease; Parkinson's disease; T cell receptor repertoire; T cells; amyotrophic lateral sclerosis; brain; central nervous system; clinical trials; conference proceedings; epilepsy; immunotherapy; major histocompatibility complex peptidome; single‐cell RNA sequencing; spinal cord; viral infection.

Abstract

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