Alzheimer's Disease: Type 3 Diabetes?

The idea is starting to get popular among Alzheimer's researchers.  Other studies link Alzheimer's disease (AD) to neuronal insulin resistance, and still others postulate the cause and effect in the opposite direction.  But a considerable and growing amount of research is beginning to identify the disease with diabetes itself, even calling for it to be renamed to "type 3 diabetes".

I'll let this research stand on its own if you want to read some of it, which I highly recommend, and I'm going to move on to some specific details of interest here.  First, one of the hallmark features of AD is evidence of "chronic oxidative stress" in and around affected neurons.  I've mentioned before, and I'll cover it in more detail later, that the free oxygen radicals that cause this damage are produced as byproducts of glucose metabolism, and that without dietary carbohydrates, the problem is avoided.  From the same article:

[I]mpairments in cerebral glucose utilization and energy metabolism represent very early abnormalities that precede or accompany the initial stages of cognitive impairment. This concept truly warrants revisiting, particularly in light of the emerging evidence that impaired insulin signaling may have an important role in the pathogenesis of AD.

This sounds a lot like stuff we've talked about before, doesn't it?  We then learn, from the this article, that "high concentrations of insulin affect the function and survival of neurons in culture by sensitizing them to toxin and stress-induced insults."

Perhaps the most important bit, and I'm still quoting from the same article but the information is easily found elsewhere, is:

Physiological insulin levels promote Aβ clearance by peptide degradation, a mechanism that involves insulin degrading enzyme (IDE) activity. A low level of insulin in brain reduces Aβ release from intracellular to extracellular compartments and high levels reduce Aβ degradation in the extracellular compartment.

That Aβ business is amyloid beta, what amyloid plaques are made of in the brains of Alzheimer's patients.  Read it again if you need to.  Insulin appears to be responsible for regulating the cleanup of amyloid plaques, which practically are Alzheimer's disease.  Too much insulin (generally a consequence of too much blood glucose, a dietary problem) reduces degradation of the plaque.  Low levels of insulin downregulate the removal of Aβ from the neurons' interiors, but this is (likely) because low insulin levels reflect low glucose levels, and we've seen that glucose and/or insulin are responsible for much of the cellular damage in the first place.

We then have a clinical observation from the same paper:

[A] growing body of evidence has been developed suggesting that glucose metabolism is associated with the pathogenesis of AD, age-related cognitive decline and neuroinflamation. Intravenous insulin infusion in healthy, eugylcemic older subjects induces a facilitation of memory while it increases cerebrospinal fluid levels of Aβ. (emphasis mine)

The picture gets clearer and clearer the more we look at it.  We have physiological models of AD as an insulin resistant brain state, a mechanical model implicating insulin in the failure to rid the brain of amyloid plaques, a well-established epidemiological "link" between AD and type 2 diabetes and insulin resistance, clinical observations confirming the theories...

And we have other articles in this blog setting this up as a pixel in an even bigger picture about the role of refined dietary carbohydrates in other chronic conditions.  And we still have a long way to go.