The lipid components of the senile plaque (SP) remain largely unknown. Senile plaques were said to be enriched in cholesterol in a few studies using the cholesterol probe filipin and a histoenzymatic method based upon cholesterol oxidase activity. We provide data that strongly suggest that these results are false-positive: the SPs were still stained in the absence of the enzyme cholesterol oxidase; filipin still labeled the plaques after lipid extraction. On the other hand, resorufin, the highly fluorescent end-product of the histoenzymatic method, bound with high affinity to the SPs and neurofibrillary tangles in a cholesterol-independent manner, and might serve as a new marker of amyloid. In conclusion, the probable cholesterol enrichment of the SPs has never been proven so far, and might necessitate non-histological methods to be ascertained.