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Table 1 Senescence-associated secretory phenotype/senescence messaging secretome biomarkers in Alzheimer's disease

From: Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases

Protein Alteration(s) in ADa Association with senescence
IL-6 ↑ in B, C, P [65, 71, 120] ↑ in oncogene-induced senescence (OIS); mediates the SASP in vitro; knockdown results in senescence bypass [59, 63]
IL-8 (CXCL8) and other CXCR2 ligands/CXCR2 ↑ IL-8 in B, C, P, focal ↑ CXCR2 in B in plaque-associated dystrophic neurites [66, 68, 69] ↑ IL-8 and other CXCR2 ligands in multiple in vitro models of replicative senescence; CXCR2 signaling functionally implicated in replicative senescence [59, 63, 64]
MCP-1 ↑ in B [65] in vitro in multiple models of replicative senescence
IL1-α ↓ in P [71], P [121, 122], ↑ mRNA in B [123] Implicated in endothelial cell senescence [124, 125]
ICAM-1 ↑ in B, P [71, 126128] in vitro in replicative senescence [63]
IGFBP ↑ IGFPB6 in P [71], ↑ IGFPB2 and 6 in C [129] Various IGFBP ↑ in replicative senescence; IGFBP sufficient and required for replicative senescence in various models [130133]
GM-CSF to ↑ in C [134, 135] in vitro in replicative senescence [63]
Osteoprotegerin ↑ in P [136] in vitro in replicative senescence [63]
PAI-1 CNS homolog neuroserpin ↑ in B [137] in vitro in models of replicative senescence and critical for induction [138]
TGF-β ↑ in B, C, P [38, 139] in vitro in multiple models of replicative senescence; implicated in inducing replicative senescence [140, 141]
WNT2 Wnt pathway implicated in pathogenic signaling cascades in AD. No rigorous biomarker studies. Aβ implicated as blocking Wnt signaling [142] ↓ WNT2 in replicative senescence and OIS [143]
sPLA2/sPLA2R ↑ group IV isoform of phospholipase A(2) in B [144] ↑ sPLA2/sPLA2R in replicative senescence; sPLA2 (PLA2G2A) can induce senescence in vitro [145]
IGF-1 Some reports indicate ↑ in AD brain [146] Linked to life-span extension [58, 60]
MMPs Various MMPs ↑ in B and P [147] MMP3 ↑ associated with replicative senescence [148]
  1. aB, brain; C, cerebrospinal fluid; P, plasma. Up and down arrows indicate increased and decreased levels, respectively. AD, Alzheimer's disease; CNS, central nervous system; GM-CSF, granulocyte-macrophage colony stimulating factor; ICAM, intracellular adhesion molecule; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; IL = interleukin; MCP, monocyte chemoattractant peptide; MMP, matrix metalloproteinase; OIS, oncogene-induced senescence; PAI, plasminogen activator inhibitor; sPLA2, soluble phospholipase A2; SASP, senescence-associated secretory phenotype; sPLA2R, soluble phospholipase A2 receptor; TGF, transforming growth factor.