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Intrathecal inflammation precedes development of Alzheimer’s disease
  1. E Tarkowski1,2,
  2. N Andreasen4,
  3. A Tarkowski1,
  4. K Blennow3
  1. 1Department of Rheumatology, University of Göteborg, Göteborg, Sweden
  2. 2Department of Geriatrics, University of Göteborg
  3. 3Department of Clinical Neurosciences (Section of Neurochemistry), University of Göteborg and Department of Clinical Chemistry, University of Göteborg
  4. 4Karolinska Institut, NEUROTEC, Department of Clinical Geriatrics, Stockholm, Sweden
  1. Correspondence to:
 Dr E Tarkowski, Department of Rheumatology, Guldhedsgatan 10, S-413 46 Göteborg, Sweden; 
 elisabeth.tarkowski{at}immuno.gu.se

Abstract

Objectives: To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1β (IL1β), tumour necrosis factor α (TNFα), GM-CSF, of the anti-inflammatory cytokine TGFβ, of tau protein, a marker for neurodegeneration, and of β amyloid (Aβ), 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 TNFα, IL1β, GM-CSF, TGFβ, βa, 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 TNFα and tau protein and significantly lower levels of TGFβ and Aβ 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 TNFα than controls. In addition, reduced CSF-Aβ42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Aβ is an early finding in AD.

Conclusions: These results demonstrate increased production of the proinflammatory cytokine, TNFα and decreased production of the anti-inflammatory cytokine TGFβ 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.

  • Alzheimer’s disease
  • mild cognitive deficit
  • cytokines
  • AD, Alzheimer’s disease
  • CSF, cerebrospinal fluid
  • IL, interleukin
  • TNF, tumour necrosis factor
  • IL1ra, IL1 receptor agonist
  • Aβ, β amyloid protein
  • MMSE, mini-mental state examination
  • MCI, mild cognitive impairment
  • ELISA, enzyme linked immunosorbent assay
  • SP, senile plaque
  • APP, amyloid precursor protein
  • VEGF, vascular endothelial growth factor

https://doi.org/10.1136/jnnp.74.9.1200

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    Footnotes

    • Funding: this study was supported by grants from the Göteborg Medical Society, University of Göteborg, The Swedish Association against Rheumatism, the King Gustaf V’s 80-year Foundation, Stroke Foundation, Gamla Tjänarinnor Foundation, John and Brit Wennerströms Foundation, Rune and Ulla Amlöv Foundation, Konrad and Helfrid Johanssons Foundation, Loo and Hans Ostermans Foundation, Clas Groschinsky Foundation, Wilhelm and Martina Lundgrens Foundation, Alzheimer’s Foundation, the Swedish Association of Neurologically Disabled, the Swedish Heart-Lung Foundation, the Swedish Society of Medicine, and the Swedish Medical Research Council (grants numbers 11560 and 12103).

    • Competing interests: none declared.