Pathology done! Now lets know about its pharmacology here :)
To treat the AD in this condition, we first have to take measures to lower down the cholesterol levels (periphery) which itself would lead to alleviation of symptoms of Alzheimer's!
High cholesterol itself suggests we have to block the pathway of its biosynthesis. For that purpose the most important step is the rate- limiting step involving reduction of HMG- CoA to form mevalonic acid (mevalonate pathway) and the enzyme that aids the process, the HMG- CoA reductase. Inhibition of this enzyme blocks this step. The HMG- CoA reductase enzyme inhibitors, famous for the name "Statins" have been used for lowering cholesterol levels since ages now. The list includes Lovastatin, Simvastatin, Atorvastatin, Pravastatin, etc.
The second class of drugs are sterol- extracting drugs like methyl beta cyclodextrin, which are the compounds employed for the preparation of cholesterol- free products. The beta- isomers consist of a 7- membered sugar ring molecule. The bulky and hydrophobic cholesterol molecule gets easily lodged inside cyclodextrin rings that are then removed. Methylated forms are more efficient in this process.
> Acute reduction of cholesterol levels by these drugs leads to reduction in the production and toxicity of amyloid beta peptide.
In Alzheimer's disease, a significant reduction of cholesterol levels in the whole-brain raft and in the white matter (mainly the hippocampus region) is observed while an increase in the levels in nerve terminals (sites rich in amyloid plaques). The low levels may be due to increased CYP46 activity leading to cholesterol oxidation and excretion. Thus CYP46 enzyme inhibitors could possibly prevent further complications!
Also "lifestyle modifications" are a must and should always be the primary measure of preventing hypercholesterolemia.
Thank you :)
- Jaskunwar Singh