Cholesterol and Alzheimer s disease

Wolo2in, B. Cholesterol and Alzheimer s disease. Biochem. Soc. Trans. 30, 525-529, 2002. 

Initial interest in cholesterol and Alzheimer s disease stemmed from a lengthy historical backdrop. One of the first studies hnking cholesterol to AD stemmed from an observation that senile plaques were quite prevalent in the brains of non-demented patients who had died from coronary heart disease [21], a population known to possess elevated cholesterol levels. Additional studies soon followed demonstrating that the ApoE4 allele of the ApoE cholesterol transporter was a major risk factor for AD [ 13 -16]. Is there a clear association between cholesterol and Alzheimer s disease ... 

Simons M, Keller P, Dichgans J, et al. Cholesterol and Alzheimer s disease. Is there ahnk Neurology 2001 57 1089-1093. 

Cutler, R. G., Kelly, J., Storie, K. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer s disease. Proc. Natl Acad. Sci. U.S.A. 101 2070-2075,2004. 

Austen, B., Christodoulou, G., Terry, J.E. (2002) Relation between cholesterol levels, statins and Alzheimer s disease in the human population. J. Nutr. Health Aging, 6, 311-3S2. 

Wang, B., Zhang, C., Zheng, W., et al. (2004) Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer s disease in Chinese. Neurosci. Lett, 14, 104-107. 

The statins may lower the risk of CHD by decreasing inflammation, an important component of atherogene-sis. Lovastatin decreased elevated plasma levels of C-reactive protein, a marker for cellular inflammation, and acute coronary events in patients with relatively low plasma cholesterol levels. Recent studies also suggest that use of statins may decrease the risk of stroke, dementia, and Alzheimer s disease and may improve bone... 

Casserly 1, Topol E (2004) Convergence of atherosclerosis and Alzheimer s disease inflammation, cholesterol, and misfolded proteins. Lancet 363 1139-1146... 

Chauhan NB (2003) Membrane dynamics, cholesterol homeostasis, and Alzheimer s disease. J Lipid Res 44 2019-2029... 

Notkola IL, Sulkava R, Pekkanen J, et al. Serum total cholesterol, apolipoprotein E4 allele, and Alzheimer s disease. Neuroepidemiology... 

Kirsch C, Eckert GP, Muller EE (2003) Brain cholesterol, statins and Alzheimer s Disease. Pharmacopsychiatry 36(Suppl 2) S113-S119... 

Harris JR, Milton NG. Cholesterol in Alzheimer s disease and other amyloidogenic disorders. SubceU Biochem. 2010 51 47-75. 

Fig. 10.5 Apolipoprotein E (APOE)-relsled serum levels of APOE, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density hpoprotein (LDL) cholesterol, amyloid- 3 peptide (1 2), and histamine in Alzheimer s disease. (Adapted from refs. 12,59, and 289.)...

Poirier, J. (2005) ApoUpoprotein E, cholesterol transport and synthesis in sporadic Alzheimer s disease. Neurobiol. Aging, 26, 355-361. 

Genes coding for APO-E are associated with different risks for Alzheimer s disease. There are three alleles (or copies) of the gene coding for this apolipoprotein which are called E2, E3, and E4. For example, a gene on chromosome 19 that codes for APO-E is linked to many cases of late-onset Alzheimer s disease. Moreover, APO-E is associated with cholesterol transport and involved with other neuronal functions, including repair, growth, and maintenance of myelin sheaths and cell membranes. 

Figs. 12—16 to 12—22) and prevent the progressive course of Alzheimer s disease. Direct inhibition of gene expression for the biosynthesis of these proteins is not currently possible and is currently not a very feasible therapeutic possibility. Perhaps a more realistic therapeutic possibility would be to inhibit the synthesis of beta amyloid, in much the same way that lipid-lowering agents act to inhibit the biosynthesis of cholesterol in order to prevent atherosclerosis. This could be done by means of enzyme inhibitors, such as protease inhibitors, which are at least a theoretical possibility. 

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