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.

Pocchiari et al. Genome Medicine 2009 1:63   doi:10.1186/gm63