Beyond Cholesterol: Statin Benefits in Alzheimer's Disease

Early epidemiological studies first implicated that cholesterol lowering treatments, such as statins, may be preventative in the development of dementia. While early studies raised significant hopes, more recent epidemiological studies suggest a more complex association between cholesterol, statin use and AD. Despite the controversy, prospective randomized placebo control studies in AD do support cognitive benefit from statin treatment. The management of cholesterol within the brain differs significantly from peripheral compartments and recent data support statin effects on brain cholesterol intracellular trafficking and plasma membrane redistribution. Thus, statin-induced cognitive alterations may occur through subtle changes in cholesterol endocytic transport mechanisms as well as through mechanisms completely independent of cholesterol modification. The current treatise examines the convergence of cholesterol and APP processing and proposes a model to highlight how cholesterol and statin modulation might impact generation of amyloidogenic Aβ peptide fragments in the brain. In addition, the present treatise reviews effects of atorvastatin on non-cholesterol, inflammatory endpoints including IL-3, IL-13 and serum amyloid P. Results suggest that IL-3, IL-13 and serum amyloid P endpoints alter following atorvastatin treatment suggesting statins may have mechanistic utility beyond cholesterol lowering.