Alzheimer’s Disease, Cholesterol, and Statins: The Junctions of Important Metabolic Pathways

Abstract

Recent years have seen a significant increase in published data supporting the positive effects of statins on neurodegenerative diseases, in particular on Alzheimer's disease. Statins show neuroprotective activity by a combination of different cellular and systemic mechanisms that are based on the inhibition of the biosynthesis of cholesterol and isoprenoid by-products. The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials. Nevertheless, these results make statins valuable assets for disease prevention rather than therapeutic agents for use when disease symptoms are already displayed. Thus, the modulation of midlife cholesterol and/or statin administration prior to the appearance of dementia or cognitive impairment may have a better long-term outcome.

Dieta mediterránea y sus efectos benéficos en la prevención de la enfermedad de Alzheimer

“…Los radicales libres y las especies reactivas del oxígeno que se generan en el organismo son neutralizados normalmente por moléculas endó-genas 33 , sin embargo, este balance antioxidante se altera en patologías relacionadas con la edad 40 , como la EA, favoreciendo una mayor producción de especies oxidativas las cuales se asocian con daño neuronal 32 , peroxidación lipídica y oxidación de enzimas relacionadas con la mantención de funciones de las neuronas y la glia 41 .…”

“…Junto con ello, este péptido es capaz de inhibir la cadena respiratoria, promoviendo disfunción mitocondrial y disminución de los niveles de ATP, desestabilizando los mecanismos de defensa antioxidante 40 .…”

Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity

“…Cholesterol is the main sterol in animal tissues, and has very important functions, as being a major component of eukaryotic membranes, and function as a biosynthetic precursor of important bioactive molecules such as steroid hormones and bile acids [83]. And also it has been shown that cholesterol can directly modulate the processing of APP [84,85].…”

“…Accordingly, it has been reported that, increased cholesterol levels enhance β and γ-secretase activity therefore, promoting APP metabolism by the amyloidogenic pathway. Conversely a decrease in intracellular cholesterol, leads to structural rupture of the lipid rafts, favoring α-secretase non-amyloidogenic APP cleavage, leading to a significant decrease in Aβ levels [83].…”

“…Hypercholesterolemia is associated with the formation of atheroma plaques that progressively could cause ischemic brain damage. Brain ischemia induce an increase in APP expression, and damages the BBB [83], and as a result the clearance of cerebral Aβ is affected (Figure 4). Moreover, Aβ could be also removed by efflux through the low density lipoprotein receptor (LRP) at the blood brain barrier (BBB).…”