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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.