Although this is a mouse study, if true in humans, it would turn around the conversation a bit.
Several epidemiological studies support the hypothesis that diabetes increases a person's risk for developing Alzheimer's disease. However, new research from the Icahn School of Medicine at Mount Sinai published in the journal Alzheimer's and Dementia suggests the reverse -- that Alzheimer's disease (AD) impairs insulin signaling in the portion of the brain responsible for regulating metabolism, making a person with AD more likely to develop diabetes. Findings also indicate that an increase of a particular group of amino acids in the blood could serve as a biomarker of impaired brain insulin signaling.
My first reaction was, maybe the glucose-starved brain is actually turning on an insulin pathway to get more glucose?
But the abstract says that they hypothesize amyloidosis is gumming up the works.
We hypothesized that cerebral amyloidosis impairs central nervous system control of metabolism through disruption of insulin signaling in the hypothalamus, which dysregulates glucose and BCAA homeostasis resulting in increased susceptibility to diabetes.
Ok, we don't know if this is true. But if it pans out, does this mean that existing diabetes means that the slow slide has already started? I'm going to assume not; it would probably work both ways. Not all diabetics wind up with AD. So I'm doing as much as I can think of to beat down the insulin resistance, but probably still need to up my game.
Any clues what would work to specifically reduce insulin resistance in the brain?
Don't panic, (((Kayell.))) This is clearly a chicken/egg proposition AND since not everyone with diabetes gets AD, there appears to be an opportunity for diet/lifestyle intervention. My understanding is that all of the strategies we employ to prevent diabetes would also benefit the brain.
1. These mice have APP/PS1 mutations, which represent 1% of all Alzheimer's disease cases. These type of mice often show Alzheimer's pathology at 5-6 months, the age tested. Despite being the mouse equivalent of "30 years old" that would mean they are like 50 year-old early on-set AD patients in terms of plaque.
2. These mice have mouse apoE, which is functionally worse than human apoE4.
3. These mice were fed a diet with 60% of calories from fat, 20% calories from carbohydrates (probably sucrose and maltodextrin), and 20% from protein which will make mice tremendously fat. Mice on a control (i.e., high carb) diet do not gain weight, even with massive quantities of sucrose. Mice are quite different from people in this regard.
4. There is a weird divergence in the epidemiological data for Alzheimer's and diabetes. Mid-life obesity is associated with AD, but late-life underweight is associated with AD. Nobody knows what happens in between. Do the obese people become thin when they get AD? Are they two completely different sets of people with different disease etiologies?
Moderator note - I deleted the attached paper (10.1016/j.jalz.2016.01.008) because our copyright infringement policy prohibits it. Members in jurisdictions for which access to Sci-Hub is legal may want to search for the paper there.
Until now, we always assumed that obese people get type 2 diabetes and then are more likely to get dementia -- we now show that actually it also works the other way around.
Its a mouse study and type 2 diabetes occurs in people as young as teenagers who clearly don't have dementia.... but an interesting avenue of research.
