Abstract
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.
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References
Adams C, Bayliss O (1975) Lipid Histochemistry. In: Glick D, Rosenbaum R (eds) Techniques of biochemical and biophysical morphology. Wiley, New York, pp 100–156
Black SL, Stanley WA, Filipp FV et al (2008) Probing lipid- and drug-binding domains with fluorescent dyes. Bioorg Med Chem 16:1162–1173
Burns MP, Noble WJ, Olm V et al (2003) Co-localization of cholesterol, apolipoprotein E and fibrillar Abeta in amyloid plaques. Brain Res Mol Brain Res 110:119–125
Deraeve C, Pitie M, Meunier B (2006) Influence of chelators and iron ions on the production and degradation of H2O2 by beta-amyloid–copper complexes. J Inorg Biochem 100:2117–2126
Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12:105–112
Liao L, Cheng D, Wang J et al (2004) Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem 279:37061–37068
Masliah E, Mallory M, Deerinck T et al (1993) Re-evaluation of the structural organization of neuritic plaques in Alzheimer’s disease. J Neuropathol Exp Neurol 52:619–632
Mori T, Paris D, Town T et al (2001) Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice. J Neuropathol Exp Neurol 60:778–785
Opazo C, Huang X, Cherny RA et al (2002) Metalloenzyme-like activity of Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2. J Biol Chem 277:40302–40308
Puglielli L, Friedlich AL, Setchell KD et al (2005) Alzheimer disease beta-amyloid activity mimics cholesterol oxidase. J Clin Invest 115:2556–2563
Simons M, Keller P, De Strooper B et al (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 95:6460–6464
Strittmatter WJ, Saunders AM, Schmechel D et al (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90:1977–1981
Tanzi RE, Bertram L (2001) New frontiers in Alzheimer’s disease genetics. Neuron 32:181–184
Thal DR, Ghebremedhin E, Haass C, Schultz C (2002) UV light-induced autofluorescence of full-length Abeta-protein deposits in the human brain. Clin Neuropathol 21:35–40
von Braunmühl A (1957) Alterserkrankungen des Zentralnervensystems. Senile Involution. Senile Demenz. Alzheimersche Krankheit. In: Lubarsch O, Henke F, Rössle R (eds) Handbuch der speziellen pathologischen Anatomie und Histologie. Springer, Berlin, pp 337–539
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Lebouvier, T., Perruchini, C., Panchal, M. et al. Cholesterol in the senile plaque: often mentioned, never seen. Acta Neuropathol 117, 31–34 (2009). https://doi.org/10.1007/s00401-008-0448-1
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DOI: https://doi.org/10.1007/s00401-008-0448-1