"Increasing evidence links cholesterol with the pathophysiology of AD. Most of the work has focused on links showing that cholesterol levels modulate Abeta production, but few papers have clearly shown abnormalities in cholesterol metabolism associated with AD. (Although one could consider ApoE4 as an abnormality in cholesterol metabolism, most data suggest that it is the ApoE4 protein, rather than the associated increase in plasma cholesterol, that is the problem). This paper is interesting because it directly links elevated cholesterol with tangle formation. The paper is also interesting because it is the first to link increases in cholesterol with pathology in the brains of patients with AD. Most other studies examining total brain cholesterol levels have yielded ambiguous results, but this paper suggests that looking directly at pathology can provide the direct link between pathophysiology of cholesterol and pathophysiology of AD."

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