. Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease. Neuron. 2003 May 22;38(4):547-54. PubMed.


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  1. These are really exciting results, and we are likely looking at a historical crucial manuscript providing the proof-of-principle that a cure for AD is possible, and definitively establishing the amyloid hypothesis for AD.


    Please see my letter to Neuron editor regarding the article by Hock
    et al.

    Science SAGE KE (26 May 2003) [ Full
    ] [ No-registration
    access link
    ] .

  3. This paper was interesting, but I find several problems with it.

    First, there was no control group that was not immunized, and the rate of increase in antibody levels was not studied in the patients prior to baseline. Thus, since some patients had endogenous antibodies to β amyloid, there was no evidence that the immunizations actually caused the increase in antibodies.

    Since a large portion of the patients did not generate a significant increase in antibody levels, and these patients did worse than the literature average on some cognitive tests, this calls into question several things:

    1) Perhaps the immunization is doing harm in some and is benefiting others,

    or, what I consider more likely:

    2) The level of antibody increase may simply be gauging the health of the immune system, and thereby gauging general health. Those who have the lowest response, then, have worse-than-average general health and thus would suffer a worse-than-average cognitive decline.

    A control of non-immunized subjects is absolutely necessary to judge how the immunization actually influenced antibody levels.

    Finally, the authors conclude that there is no evidence that the β amyloid was being bound and transported out of the brain; therefore, it is quite clearly not a clinical confirmation that β amyloid has a central role in AD, as they write.

    In fact, it seems to be suggestive that a third factor not involving β amyloid was causing the rise in antibodies as well as the increased performance—namely, the multiplicity of factors involved in immune function that are also involved in general health.

    I cite this study and discuss it in my article, "Myth: Cholesterol Causes Alzheimer's Disease | Part I: Debunking the Myth," which is located at http://www.cholesterol-and-health.com/Cholesterol-Alzheimers.html.