Table 1.
Biomarkers of neurodegeneration and neuroinflammation in Multiple Sclerosis, Parkinson, and Alzheimer's diseasea.
| Disorder | Biomarker type | Current biomarkers | Inflammatory biomarkers | Neurodegeneration biomarkers | AUC | |
|---|---|---|---|---|---|---|
 |
MS | Clinical | Neurological disability | Relapse | EDSS progression | – |
| Imaging | MRI w/gadolinium | 11C-PK11195 PET (mainly plaques) (Inglese and Petracca, 2013) | Brain atrophy (MRI); 11C-flumazenil PET (Inglese and Petracca, 2013) | – | ||
| Serum | – | TNFα, IL-1β, RANKL, IL-17, PTX3, IL-10 (D'Ambrosio et al., 2015); OPN (Housley et al., 2015) | Nfl (Zetterberg, 2017); Nfh (Housley et al., 2015) | Nfl (0.663) (Novakova et al., 2017b); IFNγ (0.91) (Arellano et al., 2017) | ||
| CSF | Oligoclonal bands; IgG index | CHI3L1 (Novakova et al., 2017a); CXCL13, IL-23, IL-17, CXCL10, TNFα, TGF-β (Kothur et al., 2016); CHIT1, MCP-1, GFAP (Novakova et al., 2017a); sTREM2 (Zetterberg, 2017); OPN (Housley et al., 2015) | Nfl, NGRN (Novakova et al., 2017a); Nfh (Housley et al., 2015); NAA(low) (Teunissen et al., 2015) | Nfl (0.774) (Novakova et al., 2017b); CHI3L1 (0.82) (Opsahl et al., 2016); CXCL13 (0.80) (Stilund et al., 2015) | ||
| PD | Clinical | Bradykinesia; Rigidity; Resting tremor | – | Disability | – | |
| Imaging | MIBG scintigraphy; SPECT (123I-ioflupane) | 11C-PK11195 PET (midbrain/putamen) (Inglese and Petracca, 2013) | – | – | ||
| Serum | – | IFNγ, IL-1β, IL-2, IL-3, IL-10, MIF, TNFα (Rocha et al., 2015); α-syn specific T-cells (Sulzer et al., 2017); N-glycated IgG (Russell et al., 2017) MIP-1β, MCP-1, IL-8 (Brockmann et al., 2017) | – | Nfl (0.91) (Hansson et al., 2017); IL-8 (0.895), MCP-1 (0.736); MIP-1β (0.767) (Brockmann et al., 2017); N-glycated IgG (0.92) (Russell et al., 2017) | ||
| CSF | – | β2-microglobulin, IL-8, IL-6, TNFα, CHI3L1 (Andersen et al., 2017) | Dopamine (loss), Nfl (low) (Andersen et al., 2017) | TNFα (0.658) (Delgado-Alvarado et al., 2017) | ||
| AD | Clinical | Progressive episodic memory loss | – | Loss of autonomy | – | |
| Imaging | PET-PiB; MRI | 11C-PK11195 PET (temporo-parietal cortex) (Inglese and Petracca, 2013) | MRI; 11C-flumazenil PET (Pascual et al., 2012) | – | ||
| Serum | - | CHI3L1 (Olsson et al., 2016); IL-8 (Popp et al., 2017); FGF-1, IL-1β, IL-10, IL-11, IL-18 (Brosseron et al., 2014), IL-3, MCP-1, RANTES, sIL-6R, TGF-β1 (Delaby et al., 2015); sCD40L (Yu et al., 2016) | Total tau (Olsson et al., 2016); NSE (Huynh and Mohan, 2017) | IL-8 (0.599), IL-3 (0.549), MCP-1 (0.501), RANTES (0.556), sIL6-R (0.595), TGF-β1 (0.567) (Delaby et al., 2015); sCD40L (0.824) (Yu et al., 2016) | ||
| CSF | Aβ1−42; total tau; p-tau | CHI3L1, MCP-1 (Olsson et al., 2016); IL-15, sFLT-1, sICAM-1 (Popp et al., 2017), MIP-1β, MIP-3β, sIL-6R (Delaby et al., 2015); IL-1β (Hesse et al., 2016) | VILIP-1 (Huynh and Mohan, 2017); NGRN (Novakova et al., 2017a); Nfl, NSE, HFABP (Olsson et al., 2016); | MCP-1 (0.503), MIP-1β (0.655), MIP-3β (0.727). p-tau (0.946), sIL-6R (0.755), tau (0.942) (Delaby et al., 2015); CHI3L1 (0.75) (Paterson et al., 2016); IL-8 (0.614) (Delaby et al., 2015); IL-1β (0.62) (Hesse et al., 2016) |
The table above is not intended as an exhaustive review. Only markers studied in human subjects were included. No animal or ex-vivo data was considered. Only one PET ligand per molecule was considered (e.g., other ligands for TSPO or amyloid exist). AUC of inflammatory biomarkers indicated when available (values are highly cohort specific and vary according to disease, test sample and quantification method). AD, Alzheimer's Disease; AUC, Area Under Curve; 11C-PK11195, a TSPO radioligand reflecting microglial activation; CHI3L1, chitinase-3-like protein 1; CHIT1, chitotriosidase; CXCL13, C-X-C motif ligand 13; EDSS, Kurtzke Expanded Disability Status Scale; FGF, fibroblast growth factor; GFAP, glial fibrillary acidic protein; HFABP, Heart fatty acid binding protein; MCP-1, monocyte chemoattractant protein-1; MIBG, metaiodobenzylguanidine; MIP, Macrophage Inflammatory Proteins; MRI, magnetic resonance imaging; MS, Multiple Sclerosis; NAA, N-acetylaspartate; Nfl, neurofilament light chain protein; Nfh, neurofilament heavy chain protein; NGRN, neurogranin; NSE, neuron-specific enolase; OPN, osteopontin; PD, Parkinson's Disease; PET, Positron Emission Tomography; PiB, Pittsburgh compound B; PTX3, pentraxin 3; RANKL, receptor activator of nuclear factor kappa-B ligand; SPECT, Single-photon emission computed tomography; sFLT-1, soluble fms-related tyrosine kinase 1; sICAM-1, soluble intercellular adhesion molecule 1; sIL-6R, Soluble Interleukin-6 receptor; sTREM2, secreted form of the triggering receptor expressed on myeloid cells 2; TGF-β1, transforming growth factor beta 1; VILIP-1, Visinin-like protein 1.