Alzheimer’s disease cholesterol

Mathew A, Yoshida Y, Maekawa T, Kumar DS (2011) Alzheimer s disease Cholesterol a menace Brain Res Bull 86 1-12... 

ADCLT Alzheimer s Disease Cholesterol Lowering Trial... 

KEY EXPERIMENT ALZHEIMER S DISEASE, CHOLESTEROL, AND STATINS WHERE IS THE LINK ... 

Apolipoprotein E (ApoE) A protein involved in cholesterol transport that has three major isoforms, one of which, ApoE4, significantly increases the risk of developing Alzheimer s disease. 

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. 

Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, et al. 2001. On the turnover of brain cholesterol in patients with Alzheimer s disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 314 45-48. 

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.)...

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. 

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

Kovacs DM, Tanzi RE, Puglielli L. (2003) Alzheimer s disease The cholesterol connection. Nat Neurosci 6 345-351. 

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... 

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

Amyloid cascade hypothesis of Alzheimer s disease. A leading contemporary theory for the biological basis of Alzheimer s disease centers around the formation of beta amyloid. Certainly much of this amyloid destroys cholinergic neurons in the nucleus basalis of Meynert (Fig. 12—11), although the damage becomes more widespread as the disease progresses (Fig. 12-13). Hypothetically, Alzheimer s disease is a disorder in which beta amyloid deposition destroys neurons, in a manner somewhat analogous to that in which the abnormal deposition of cholesterol causes atherosclerosis. Thus,... 

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. 

Sparks DL. Coronary artery disease, hypertension, ApoE, and cholesterol A link to Alzheimer s disease Ann N Acad Sci 1997 826 128-146. 

Eckert G.P., Kirsch C., Muller W.E. Brain-membrane cholesterol in Alzheimer s disease. J. Nutr. Health Aging 2003,7 1 -23. 

---