We know that there is a strong correlation between insulin resistance and early Alzheimer's, and also there is an association between mitochondrial dysfunction (particularly in complex 1) and Alzheimer's. As I discussed in Basic Science: Energy is Everything and Brain Efficiency, when the mitochondria aren't happy, your brain isn't happy. Mitochondrial dysfunction is also implicated in Parkinson's Disease and ALS, both long-term and ultimately fatal degenerative conditions.
And now, a point I've made before (in Low Cholesterol and Suicide)- the brain is relatively small, but has 25% of the body's cholesterol. Cholesterol insulates neurons as part of the myelin sheath and provides the scaffold for the neural network, and is an important part of the membranes and all synapses. While much of the cholesterol used in the brain is made in the brain, there is clear evidence that apolipoprotein E (ApoE) is a big player in the game of shuttling cholesterol, fat, and antioxidants to the central nervous system from the body's main cholesterol factory, the liver. ApoE is made in nerve cells called astrocytes (who tend to and feed neurons), and ApoE allows the astrocytes to suck lipids, antioxidants, and cholesterol arriving in LDL and IDL particles from the bloodstream. Yes, astrocytes can transport LDL across the blood brain barrier.
The biggest genetic risk for Alzheimer's is being a carrier of a certain type of ApoE gene called ApoE4. Research has shown that ApoE4 is associated with reduced cholesterol uptake by the astrocytes. What has been confusing for the lipophobic medical establishment is that ApoE4 is associated with high LDL cholesterol… so it must be that nasty horrible LDL killing the brain! But the key bit to understand is that LDL cholesterol in longitudinal studies tends to drop before the development of Alzheimer's disease. Hmmm. We can't ignore the following tantalizing clue either:
…high cholesterol level is positively correlated with longevity in people over 85 years old, and in some cases has been shown to be associated with better memory function and reduced dementia… the cerebrospinal fluid of [Alzheimer's Disease] patients is substantially depleted in lipoproteins, cholesterol, triglycerides, and free fatty acids compared to matched controls.All of us, but especially readers of a since-removed blog post that was part of the Venus-gate paleo disruption of a few weeks ago about the supposed dangers of densely packed saturated fat should have an understanding of how lipoproteins work. Lipoproteins (such as HDL, LDL, chylomicrons, and VLDL) basically look like this:
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| Image from Wikipedia |
Lipoproteins carry fats and other delicacies through the blood. The blood is dangerous and filled with nasty things like oxygen and iron that can break down our gentle fats. We don't want our fats oxidized - so the lipoproteins tuck the fats into the inside to keep them safe and snuggly. Again, a MAJOR REASON for the particular structure of lipoproteins is to keep those fats safe and not exposed to the blood. Once fats are delivered to cell membranes, we still want to keep them safe - and cholesterol is like a bit of plate armor - it helps the fats stack more tightly, protecting them from oxidative damage and invading microbial pathogens.
Seneff et al continue to stack the evidence in their paper - dietary avoidance of fat (replaced by carbohydrate) and the increasingly zealous prescriptions for cholesterol-lowering medication has coincided with the rise in Alzheimer's Dementia and diabetes and obesity. These are only correlations, but one might consider that to be some evidence in favor of the plausible hypothesis that stripping the brain of cholesterol especially in an oxidative, hyperglycemic environment could lead to very sick neurons.
