Cholesterol in the CNS: Right Place At The Right Time

Cholesterol is indispensable to the brain and nerves.  Native non-oxidized cholesterol is much more important to the nervous system than other organ systems for which such normal levels of cholesterol may be excessive in that system.  So much so that the brain has its own isolated supply separated from the blood by the notoriously hard to cross blood brain barrier (BBB) which relies on collagen to make it selectively impenetrable to certain molecules.  Any excess is turned into a hydroxy- soluble form which is released from the brain into the blood circulation.  However, when it runs low for whatever reason, cholesterol can be and is actively transported across the BBB from the hepatic supply.  Nowdays, the statin industry has introduced some confusion by entering into the science of Alzheimer's disease.  The big million dollar question is how interfering with the mevalonate pathway can help reduce the causal protein tangles when lowering cholesterol below normal is very toxic to neural function.  There are some elucidations regarding isoprenoids involvement, independent of cholesterol.  Perhaps in some instances with specific ApoE isoforms this is true, but in the majority of instances lowering CNS cholesterol damages it instead of benefitting it.  The tangible outcome of cholesterol depletion in the human brain are problems like amnesia, and the very symptoms of Alzheimer's itself.  The question to answer is probably what optimal cholesterol synthesis is to the brain, as compared to that in the blood supply, just as the "normal" brain ascorbate pool (2000-10,000uM)  is much much higher than that of the bloodstream (60-150uM).

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