While this paper is definitely of interest, I found some fault with their treatment of amyloid theory. The authors note in the abstract that they significnatly reduced "total amyloid," but they do not note that insoluble amyloid was not significantly reduced. There was a modest decline seen when the data was taken in aggregate, but the p value was .50, ten times the probability due to chance that is acceptable to report a finding. Thus, it should have been emphasized that the decrease in amyloid plaque had a relationship only to insoluble beta-amyloid, and not soluble beta-amyloid. Otherwise, a false impression is given that the accumulation of beta-amyloid per se is what is driving the formation of plaques, rather than considering that DHA might be mitigating the formation of plaques from the beta-amyloid through a mechanism other than the mere production of beta-amyloid. As I point out in my latest article, this group showed last year that DHA-deficiency appears to contribute to insulin resistance...  Read more

While this paper is definitely of interest, I found some fault with their treatment of amyloid theory. The authors note in the abstract that they significnatly reduced "total amyloid," but they do not note that insoluble amyloid was not significantly reduced. There was a modest decline seen when the data was taken in aggregate, but the p value was .50, ten times the probability due to chance that is acceptable to report a finding. Thus, it should have been emphasized that the decrease in amyloid plaque had a relationship only to insoluble beta-amyloid, and not soluble beta-amyloid. Otherwise, a false impression is given that the accumulation of beta-amyloid per se is what is driving the formation of plaques, rather than considering that DHA might be mitigating the formation of plaques from the beta-amyloid through a mechanism other than the mere production of beta-amyloid. As I point out in my latest article, this group showed last year that DHA-deficiency appears to contribute to insulin resistance through the loss of P13-kinase (Colon, 2004), and Ho (2004) showed that diet-induced insulin resistance caused the relationship between gamma-secretase activity and AD-related pathology to increase. Thus, if insulin resistance and the loss of P13-kinase action increases the relationship between beta-amyloid production (marked by gamma-secretase activity) and AD-related pathology, that would seem to imply that DHA deficiency would be mediating the pathology through a mechanism related to this phenomenon rather than production of beta-amyloid per se. The authors refer in the text to beta-amyloid as "the causal factor" in Alzheimer's disease, despite that beta-amyloid has been demonstrated to have positive effects (Koudinov, 2004), despite the fact that their earlier study (Calon, 2004) was conducted on the explicit basis that memory loss is better correlated with dendritic degeneration than plaques or tangles, revealing a more complex view than "beta-amyloid causes Alzheimer's," and the present study seemed to indicate a lack of relationship between soluble beta-amyloid and pathology. In the last sentence of the abstract the authors also refer to beta-amyloid toxicity as "downstream" from production and accumulation, but mention nothing about aggregative factors and plaque formation, as if the latter were simply due to the former and nothing else. Chris Masterjohn

References:
Calon et al., (2004) “Docosohexaenoic Acid Protects from Dendritic Pathology in an Alzheimer’s Disease Mouse Model,” Neuron, Sept. 2, Vol 43, 633-645, Ho, et al., “Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease,” The FASEB Journal express article 10.1096/fj.o3-0978fje. Epub March 19, 2004. Koudinov and Koudinova, (2004) “Amyloid Beta Protein Restores Hippocampal Long Term Potentiation: A Central Role for CholesteroL?” Neurobiology of Lipids, Vol. 1 article 8.

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