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Reducing Amyloid Load to Improve Alzheimer Disease?

A promising approach showed no benefit.

A leading theory on the pathogenesis of Alzheimer disease (AD) is that overproduction of amyloid, particularly amyloid-β, is involved. Tarenflurbil, a drug that influences the production of amyloid-β through the formation of shorter, less-toxic chains, showed promise in a small clinical trial. In this larger, randomized, industry-sponsored trial, 1684 patients (mean age, 75) with mild AD received tarenflurbil or placebo. Most were taking acetylcholinesterase inhibitors, memantine (Namenda), or both.

At 18-month follow-up, the two groups did not differ in absolute levels or rates of cognitive decline nor in several secondary outcomes. The dropout rate was significantly higher in the intervention group than in the control group. Significantly more intervention patients than control patients experienced major adverse events, including anemia, pneumonia, and herpes zoster.

Comment: The lack of benefit was obviously disappointing for the investigators — and for editorialists, who noted that the most effective approach to combating AD is likely to be preventive and will need to start as early in the course of the disease as possible, ideally preclinically. This approach will require use of sensitive and specific biomarkers; leptin might be one such biomarker because high leptin levels recently were found to be associated with lower risk for AD.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine January 7, 2010

Citation(s):

Green RC et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009 Dec 16; 302:2557.

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• Medline abstract (Free)

Montine TJ and Larson EB. Late-life dementias: Does this unyielding global challenge require a broader view? JAMA 2009 Dec 16; 302:2593.

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• Medline abstract (Free)

Lieb W et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA 2009 Dec 16; 302:2565.

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• Medline abstract (Free)

Reader Remarks:

Review and add to remarks on this article

• AD prevention
  Scott C Leeth, 25 Oct 2010 1:51 PM EST
  Specialty: Family Medicine
  Alzheimers is a disease of affluence. Prevention starts at birth with a whole food plant based diet, and limiting toxin... [more]

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