Table 2.
Blood biomarkers for non ATN-processes proposed for AD dementia in DS. Biomarkers are grouped according to the molecular pathway pathologically affected in DS. Colors for each group of biomarkers are related to Figure 2.
| Affected Mechanism |
Biomarker | Matrix | Technique | Platform | Results in DS Dementia | Refs |
|---|---|---|---|---|---|---|
| Inflammatory response | IFN-γ | Plasma | Mesoscale | Multi-Spot V-Plex Pro-inflammatory Panel (MesoScale Discovery) |
DS ~ controls DS-AD > controls |
[62] |
| TNF-α | DS > controls DS-AD > controls |
|||||
| IL-6 | DS > controls DS-AD > controls |
|||||
| IL-8 | DS ~ controls DS-AD > controls |
|||||
| IL-10 | DS > controls DS-AD > controls |
|||||
| NGAL | Serum | ELISA | ELISA kit (R&D systems) ELISA reader (Asys UVM 340 Biochrom) |
Increased in DS. Association with species of Aβ depending on dementia progression | [108] | |
| NGF metabolic pathway | proNGF | Plasma | WB | Semi-dry transfer (Bio-Rad) | DS > controls DS-AD > controls |
[116] |
| neuroserpin | WB | Semi-dry transfer (Bio-Rad) | Similar levels in all groups | |||
| tPA | ELISA | tPA ELISA kit (Abcam) | DS < controls DS-AD < controls |
|||
| MMP-1 | Mesoscale | Multi-Spot MMP 3-Plex Ultra-Sensitive kit SECTOR Imager 2400 (MesoScale Discovery) |
DS > controls DS-AD > controls |
|||
| MMP-3 | DS > controls DS-AD > controls |
|||||
| MMP-9 | Similar levels in all groups | |||||
| Biogenic amines | (nor)adrenergic (NA/A, MHPG) |
Serum | RP-HPLC | AlexysTM Dual Monoamines Analyzer | Lower levels MHPG in DS dementia vs. non-demented DS and heathy controls | [118] |
| serotonergic (5-HT, 5-HIAA) | ||||||
| dopaminergic (DA, HVA, DOPAC) | ||||||
| Carbon metabolism | Lactic acid | Plasma | Targeted LC-MS/MS | Triple Quadrupole MS (Xevo-TQ-S, Waters Corporation) | DS-AD > non-AD-DS | [120] |
| Pyruvic acid | DS-AD > non-AD-DS | |||||
| Methyladipic acid | DS-AD > non-AD-DS | |||||
| Uridine | DS-AD < non-AD-DS | |||||
| Oxidative stress | SOD | Cytosolic and intracellular fractions from neutrophils | Spectro- photometry |
Hitachi U-2010 spectrophotometer | SOD activity correlates to memory functioning in DS | [122] |
| DNA alterations | Telomere length | DNA extracted from T-lymphocytes | FISH | MetaSystems ISIS Image analyzer | Shortening of telomeres changes with AD progression in DS | [123] |
| DNA mehylation | DNA extracted from whole blood | Sodium bisulfite conversion | Infinium MethylationEPIC BeadChips and Illumina iScan |
2716 differentially methylated sites in DS, 9 related to dementia. | [124] |
IL, interleukin; TNF, tumor necrosis factor; NGAL (neutrophil gelatinase-associated lipocalin); NGF, nerve growth factor; tPA, tissue plasminogen activator; MMP, matrix metalloproteinase; MHPG, 3-methoxy-4-hydroxyphenylglycol; SOD, superoxide dismutase; WB, Western blot; ELISA, enzyme-linked immunoassay; RP-HPLC, reversed phase-high-performance liquid chromatography; FISH, fluorescence in situ hybridization.