Intrathecal inflammation precedes development of Alzheimer's disease.
OBJECTIVE
To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), GM-CSF, of the anti-inflammatory cytokine TGFbeta, of tau protein, a marker for neurodegeneration, and of beta amyloid (Abeta), a protein involved in the formation of senile plaques, in prospectively followed up patients with mild cognitive impairment (MCI).


METHODS
Analyses of CSF levels of TNFalpha, IL1beta, GM-CSF, TGFbeta, betaa, and tau protein were performed using ELISA in 56 patients with MCI who were followed up prospectively and in 25 age matched, healthy controls.


RESULTS
Patients with MCI displayed significantly higher levels of TNFalpha and tau protein and significantly lower levels of TGFbeta and Abeta compared with the healthy controls. After nine months of follow up, 25 patients still displayed MCI while the remaining 31 patients had progressed to Alzheimer's disease (AD). Only MCI patients who progressed to AD at follow up, showed significantly higher CSF levels of TNFalpha than controls. In addition, reduced CSF-Abeta42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Abeta is an early finding in AD.


CONCLUSIONS
These results demonstrate increased production of the proinflammatory cytokine, TNFalpha and decreased production of the anti-inflammatory cytokine TGFbeta in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD.
Tarkowski
E
E
Department of Rheumatology, University of Göteborg, Göteborg, Sweden. elisabeth.tarkowski@immuno.gu.se
Andreasen
N
N
Tarkowski
A
A
Blennow
K
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000276:immunology*; D003072:Cognition Disorders / Q000503:physiopathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000134:cerebrospinal fluid; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid; D011446:Prospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor