Fig. 1

Proposed mechanisms of action for immunomodulatory therapeutics in Alzheimer’s disease (AD) clinical trials. Clinical stage immunomodulatory therapeutics currently being examined for AD target receptors on immune cells (e.g., peripheral myeloid cells, microglia) and immune mediators in circulation (e.g., sTNF). Drug names are listed in red. Below each drug name is the proposed mechanism of action. The immune pathways and processes affected by each drug are described in the adjacent box. Abbreviations: ACV, acyclovir; ADAM12, ADAM metallopeptidase domain 12; ADAM17, ADAM metallopeptidase domain 17; CSF1R, colony stimulating factor 1 receptor; DAP12, transmembrane immune signaling adaptor TYROBP; ERK, extracellular signal-regulated kinase; FIMP, chromosome 16 open reading frame 92; IKK, inhibitor of NF-kB kinase; IL-34, interleukin 34; IRF7, interferon regulatory factor 7; ITRAM, immunoreceptor tyrosine-based activation motif; MAPK, mitogen-activated protein kinase; MS4A, membrane spanning 4-domains; MyD88, myeloid differentiation primary response 88; NF-kB, nuclear factor kappa-light-chain enhancer of activated B cells; PKC, protein kinase C; sTNF, soluble tumor necrosis factor; STAT1, signal transducer and activator of transcription 1; STAT2, Signal transducer and activator of transcription 2; sTREM2, soluble triggering receptor expressed on myeloid cells 2; SYK, spleen associated tyrosine kinase; TLR9, Toll-like receptor 9; TNFR1, tumor necrosis factor receptor 1; TREM2, triggering receptor expressed on myeloid cells 2