Alzheimer’s is the most common dementia. For decades it was believed to be caused by buildup of amyloid beta plaque. A lot of recent research, though, has noted that there tends to be insulin deficiencies and insulin resistance in the brains of those with Alzheimer’s.

Inside the brain of someone with Alzheimer’s, neural tangles, plaques, and amyloid beta build-ups are found. This environment is not good: various neural units lose function.

But which things are causing Alzheimer’s, and which are the result? The “standard theory” for the last 25 years is that the amyloid beta buildup is the cause. However, more recent research suggests that this may not be the full picture.

Reducing Amyloid Beta Directly Has Had Little Effect

Amyloid beta is a normal brain byproduct. It is drained off during sleep by the glymphatic system. No one seems to know just what amyloid beta is for. This as already a little scary—trying to change the level of a normal body bio-chemical whose function is unknown. It surely must have a purpose. In fact, amyloid beta levels are higher in young people than in normal older people. Another strange observation is that 30% of cognitively unimpaired people have significant levels of amyloid beta plaque. What would seem to be the clincher though is that certain immunotherapy techniques—basically getting the immune system to attack and remove amyloid beta—do indeed significantly remove and reduce amyloid plaque, but these therapies have little benefit on the progress of the dementia itself.

This strongly suggests that we are looking at a symptom, but not a cause. So if we toss the “Alzheimer’s is caused by amyloid beta buildup” hypothesis out the window, what are we left with?

There is a fairly strong genetic cause called the APO-E4 variant. APO is a family of proteins that coat fat particles so that they are soluble in blood. The coating for the circulating fat from your last meal is called APO-E, and can occur in three genetically determined variants designated APO-E2, 3, and 4. Those with APO-E4 present have a much higher risk of Alzheimer’s, accounting for about 25% of the cases. This raises two immediate questions:

1. What is the cause for the other 75%?
2. What percentage of the APO-E4 get Alzheimer’s?

The answer to the second question is around a third. So APO-E4 is a factor, but can’t be the predominant one.

This would seem to implicate behavior. So to try and get at the first question, let’s turn things inside-out. Do people that get Alzheimer’s have any particular lifestyle characteristics? Turns out that Adult onset diabetics are 60% more likely to get Alzheimer’s. So here is a clue pointing to glucose management. There is another big clue that points to this also: the ketogenic diet. A ketogenic diet is one with little or no carbs. In one test, Alzheimer’s patients score 50% better on a short-term memory test after only 6 weeks on this diet. This represents some actual recovery.

At this point we have a smoking gun—sugar—and as it turns out, a recent wave of research is pointing to Alzheimer’s as a metabolism problem. In adult onset diabetes, also called type 2 diabetes, high sugar and starch intake cause cells to become insulin resistant and won’t take up sugar. This causes a permanent state of high blood sugar and high blood insulin. Something like this seems to be happening in the brain too.

Strong evidence has emerged in the last few years that Alzheimer’s is a sugar metabolism issue local to the brain. Many researchers are now calling it Type 3 Diabetes. The “new” diabetes corresponds to a chronic insulin resistance plus insulin deficiency state that is largely confined to the brain. The brain appears to have its own glucose regulation system and insulin production that is fairly separate from the rest of the body’s. How can this be?

Capillaries, which carry nutrients and hormones to and from the brain, must cross the blood-brain barrier. Small molecules like water and most gases can cross it, but it is selective with respect to larger ones. This has the effect of protecting the brain from undesirable material present in the blood, like bacteria, and it also effectively walls off and isolates the brain—creating its own environment. We don’t draw blood from this region, at least not on humans, so we really don’t know what the levels are or should be. (Well we do but that is mostly from spinal taps and this is inadequate data for broad deductions.) The idea of a separate glucose regulation for the brain makes a lot of sense. Sugar demand spikes very quickly in certain neural activities, and it would make little sense to raise glucose for the entire body. Too slow too.

So its sugar, sugar, sugar, all over again. And the reason the overlap of Alzheimer’s isn’t 100% with adult onset diabetes is because we are dealing with two different systems. One can break and the other can still work or vice versa or they can both be broken.

So the cause once again: too much sugar. Which explains why hunter-gatherers don’t get Alzheimer’s. In fact, some hunter-gatherer tribes have sky-high levels of APO-E4, and still don’t get Alzheimer’s, though they likely would pretty quickly on a western diet.

So what’s doing the damage? Ruining the neurons? It’s not the amyloid beta. It is where the removal vaccine would have worked and why it didn’t. It’s once again chronically high sugar and insulin. If that situation is reversed with the ketogenic diet, there is marked improvement, though no cure. As far as prevention: keep those glucose and insulin numbers low. How low? If observed lifelong, someone with an A1C (average glucose) of 5% or less, a fasting glucose of 80 mg/dl or less, and insulin if 8 µu/dl would be at very low risk for both Alzheimer’s and adult onset diabetes. Somewhat higher—somewhat more risk. Anyone with the APO-E4 variant, which can be determined with a blood test, had best double down.