Two apparently contradictory reports in the August 11 Lancet have injected new fuel into the debate about the role of inflammation in Alzheimer's disease.

In the first study, Willem Van Gool at the Academic Medical Center, Amsterdam, and colleages, tested the antiinflammatory drug hydroxychloroquine in a placebo-controlled trial of 168 patients with early AD. Over an 18-month period, the drug failed to slow disease progression as judged by cognitive function and deterioration in the patients' daily routines.

In the second study, Richard Banati and colleagues at the Hammersmith Hospital, London, used positron emission topography scans of patients with probable AD to estimate binding of the R-enantiomer of the ligand PK11195. The ligand serves as an in vivo marker of activated microglia, a normally dormant population of brain macrophages that are thought to mediate the inflammatory response. The researchers found significantly increased binding in the AD group compared to age-matched controls. Areas most affected included the inferior and middle temporal gyri, amygdala, and the inferior parietal lobe. Greater microglial activation was seen in the left hemisphere. In follow-up MRI scans conducted over a one- to two-year period, the researchers found that areas with greatest (R)-PK11195 binding atrophied fastest, suggesting that microglial activation had contributed to disease progression.

In an accompanying commentary, Roy Jones of St Martins Hospital, Bath, points out that the key factor in resolving these and other equivocal data on Alzheimer's and inflammation may be time, in that antiinflammatory drugs may have prophylactic benefits but may be ineffective once the disease has progressed even to early stages.—Tom Fagan


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Primary Papers

  1. . Effect of hydroxychloroquine on progression of dementia in early Alzheimer's disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet. 2001 Aug 11;358(9280):455-60. PubMed.
  2. . In-vivo measurement of activated microglia in dementia. Lancet. 2001 Aug 11;358(9280):461-7. PubMed.
  3. . Inflammation and Alzheimer's disease. Lancet. 2001 Aug 11;358(9280):436-7. PubMed.