Enrichment of cholesterol in microdissected Alzheimer`s disease senile plaques as assessed by mass spectrometry [Research Articles] (Journal of Lipid Research)

Extensive knowledge of the protein components of the senile plaques, one of the hallmark lesions of Alzheimer`s disease, has been acquired over the years, but their lipid composition remains poorly known. Evidence suggests that cholesterol contributes to the pathogenesis of Alzheimer`s disease. However, its presence within senile plaques has never been ascertained with analytic methods. Senile plaques were microdissected from sections of the isocortex in three Braak VI Alzheimer`s disease cases and compared with a similar number of samples from the adjoining neuropil, free of amyloid-β peptide (Aβ) deposit. Two cases were apo4/apo3, and one case was apo3/apo3. A known quantity of 13C-labeled cholesterol was added to the samples as a standard. After hexane extraction, cholesterol content was analyzed by liquid chromatography coupled with electrospray ionization mass spectrometry. The mean concentration of free cholesterol was 4.25 ± 0.1 attomoles/µm3 in the senile plaques and 2.2 ± 0.49 attomoles/µm3 in the neuropil (t = 4.41, P < 0.0009). The quantity of free cholesterol per senile plaque (67 ± 16 femtomol) is similar to the published quantity of Aβ peptide. The highly significant increase in the cholesterol concentration, associated with the increased risk of Alzheimer`s disease linked to the apo4 allele, suggests new pathogenetic mechanisms.