Proteomic signatures of neuroinflammation in Alzheimer’s disease, multiple sclerosis and ischemic stroke

Introduction: Inflammation is integral in the neuropathology of both chronic and acute neurological disorders. Knowing the inflammatory profile is important for clarification of disease mechanisms, diagnostic purposes, and ultimately treatment options.

Areas covered: A systematic review was performed on literature from PubMed using the search terms ‘Alzheimer’s disease’ (AD) or ”multiple sclerosis” (MS) or ”ischemic stroke” and ‘proteomics’. Inflammatory proteins were assessed in blood, cerebrospinal fluid (CSF), and post-mortem brain tissue. Regulated inflammatory proteins across compartments and disorders mainly consisted of innate immune proteins, acute phase proteins and oxidative stress response proteins. In addition, immunoglobulin chains were signature proteins of MS, reflecting additional involvement of adaptive immunity. The Chitinase 3-like protein 1 was increased in ten original articles on MS and in three on AD supporting its implication in these diseases. Furthermore, CNS/CSF AD inflammatory proteins were matched to a CNS myeloid cell proteome implicating Alpha-2-Macroglobulin and Annexin A1 in AD pathogenesis.

Expert opinion: Proteomics is an excellent technique for profiling inflammatory proteins in tissues and cells, but still targeted approaches are required for profiling of very low abundance proteins and peptides. Knowing the inflammatory signature of brain tissue, CSF, blood, and CNS myeloid cells holds the potential to point to novel mechanistic aspects of neurological diseases.