Table 1.
Markers in patients with prion diseases
| Relative levels in human prion disease compared to controls | |||||
|---|---|---|---|---|---|
| Marker | Cellular function | CSF | Plasma | Reference | Notes |
| α1-ACT | Serine proteinase inhibitor | ↑ sCJD | ↔ sCJD | [54] | Elevated in urine of sCJD and in plasma and CSF of AD |
| ↑ sCJD | NT | [63] | |||
| α-Tocopherol | Major lipophilic antioxidant | ↓ sCJD | ↔ sCJD | [64] | - |
| Apolipoprotein | Components of high density lipoprotein in plasma. Participate in PrP clustering and sequestration | ↔ sCJD | NT | [65] | Over-expression of Apo-J in CJD brains and in urine of BSE orally-infected cattle |
| ↑ vCJD compared to sCJD | NT | [66] | |||
| ↑ sCJD (A1 and A4) | NT | [63] | |||
| ↓ sCJD (Apo-J, Clusterin) | NT | [63] | |||
| Ascorbate | Major hydrophilic antioxidant | ↓ sCJD | ↓ sCJD | [64] | - |
| C-reactive protein | Markers for inflammation or tissue injury | NT | ↔ sCJD | [67] | - |
| Cystatin C | A cysteine proteinase inhibitor, mostly synthesized in the CSF; it is also localized in glial cells and neurons | ↑ CJD (not specified) | NT | [68] | Gene is upregulated in the brain of sCJD; reported normal in AD patients |
| ↑ sCJD | NT | [63] | |||
| ↑ sCJD, ↔ vCJD | NT | [54] | |||
| F2-isoprostanes | Markers of lipid peroxidation and oxidative stress in vivo | ↑ sCJD, ↑ gCJD | NT | [48] | - |
| ↔ vCJD | NT | [49] | |||
| Gelsolin | Regulator of actin filament assembly | ↓ sCJD | NT | [63] | No difference between CJD and AD |
| ↓ sCJD | NT | [46] | |||
| H-FABP | Belonging to a family of small, highly conserved, cytosolic proteins involved in fatty acid transport and metabolism | ↑ sCJD, ↑ vCJD | ↑ sCJD, ↑ vCJD | [55] | CSF of CJD taken post-mortem while in controls taken from living individuals; plasma levels do not differ between CJD and AD |
| ↑ sCJD | ↑ sCJD | [56] | |||
| ↑ sCJD | NT | [69] | |||
| Hp2-α haptoglobin | Binds hemoglobin for physiological degradation | ↑ sCJD | NT | [63] | - |
| Interleukin 1β | Pro-inflammatory cytokine, involved in immune response | ↑ sCJD, ↑ vCJD | NT | [70] | - |
| Interleukin 4 and 10 | Anti-inflammatory cytokine | ↑ sCJD | NT | [71] | Not altered in the brain of sCJD |
| Interleukin 6 | Markers for inflammation or tissue injury | NT | ↔ sCJD | [67] | - |
| Interleukin 8 | Chemokine with immunoreactive s propertie | ↑ sCJD | NT | [71] CJD | Increased in AD, but at a lower level than |
| Lactic acid | End-product of anaerobic glycolysis | ↑ sCJD | NT | [72] | Produced by LDH action on pyruvate |
| LDH | Catalyzes the interconversion between pyrvate and lactic acid | ↑ sCJD | NT | [46,47] | - |
| MDA | Marker of oxidative stress | ↔ sCJD | ↔ sCJD (serum) | [73] | Increased MDA has been reported in scrapie-infected mice |
| PGE2 | Major arachidonic acid metabolite of the cyclooxygenase pathway | ↑ sCJD, ↑ gCJD | NT | [48] | Levels of PGE2 correlate with disease duration in sCJD |
| ↑ vCJD | [49] | ||||
| TGF-β2 | Anti-inflammatory cytokine | ↓ sCJD | NT | [71] | Increased immunoreactivity in neurons of the neurocortex in 20 patients with human prion diseases |
| TNF-α | Proinflammatory cytokine | ↑ sCJD, ↑ vCJD | NT | [70] | Gene is upregulated in the brain of sCJD patients |
| Not detectable, sCJD | NT | [71] | |||
| Transferrin | Iron carrier protein in the blood | ↑ sCJD | NT | [63] | Upregulated in sera of patients with AD |
| ↑ sCJD | NT | [46] | |||
| Ubiquitin | Involved in ATP-dependent selective degradation of cellular proteins, maintenance of chromatin structure, regulation of gene expression, stress response, and ribosome biogenesis. | ↑ sCJD | NT | [63] | Elevated levels in CSF of AD patients |
| Uric acid | Non-enzymatic antioxidant in the brain | ↔ sCJD, ↓ vCJD | NT | [50] | Decreased level in the CSF in BSE-infected cattle |
Arrows indicate: up, increased; down, decreased; horizontal, equivalent. A1, apolipoprotein 1; A4, apolipoprotein 4; α1-ACT, antichymotrypsin; AD, Alzheimer's disease; Apo-J, apolipoprotein J or clusterin; ATP, adenosine triphosphate; BSE, bovine spongiform encephalopathy; gCJD, genetic Creutzfeldt-Jakob disease; sCJD, sporadic Creutzfeldt-Jakob disease; vCJD, variant Creutzfeldt-Jakob disease; CSF, cerebrospinal fluid; H-FABP, heart-2, transforming growth fatty acid binding protein; LDH, lactate dehydrogenase; MDA, malondialdehyde; NT, not tested; PGE2, prostaglandin E2; TGF-β factor-β2; TNF-α, tumor necrosis factor-α.