Immune Signaling in Neurodegeneration

Immunity. 2019 Apr 16;50(4):955-974. doi: 10.1016/j.immuni.2019.03.016.


Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. These immune signaling pathways are important under both healthy and neurodegenerative conditions, and recent work has highlighted new functional aspects of their signaling. Finally, we assess future directions for immune-related research in neurodegeneration and potential avenues for immune-related therapies.

Keywords: Alzheimer’s disease; Complement; Cytokine; GWAS; Inflammation; Innate Immunity; Microglia; Neuro-immune; Neurodegeneration; Neuroinflammation; Signaling; TGF-β; TREM2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / immunology
  • Animals
  • Complement Activation
  • Disease Progression
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Gliosis / immunology
  • Gliosis / pathology
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microglia / immunology
  • Models, Immunological
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / immunology*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / therapy
  • Protein Aggregation, Pathological / immunology
  • Receptors, Immunologic / immunology
  • Signal Transduction / immunology*
  • Transforming Growth Factor beta / immunology


  • Membrane Glycoproteins
  • Receptors, Immunologic
  • TREM2 protein, human
  • Transforming Growth Factor beta