While perusing articles this week I came across something I had to write about. It seems as thought researchers at Brown University have established a link between insulin resistance found in the brain and Alzheimer’s disease (AD). When I first read this claim, in relation to the destruction of peripheral nerves that occurs under such pathology, the brilliance of this tie was truly awe inspiring and only left me with the question: why has this taken this long to figure out?
To refresh, in diabetes, pathology of sugar utilization that leads to metabolic imbalance, the peripheral nerves begin to die off as the systemic impairment in glucose metabolism begins to intensify. Since insulin is needed to take glucose into the majority of cells, insulin resistance represents resistance to the uptake of sugar on a continuum that is at one point labeled diabetes. Since neurons are constantly being used to send sensory information and conduct back motor information, they generally tend to have a high metabolic demand. For this reason, in diabetics, the general trend is to begin losing sensory input from the most distal (furthest from heart) aspect to the most proximal (closest to heart). In fact, sugar is of such importance to neurons, that the body has developed a system of sugar balance, involving glycogen, within the brain that is sequestered from use from the rest of the body.
In Alzheimer’s disease ceramide accumulation, leading to increased inflammation and stress, has been a well established fact; the rationale that has been brought forth by this study is that dysfunctional lipid metabolism, secondary to insulin resistance, promotes ceramide accumulation and thus increases inflammation and stress. They achieved this by elucidating the correlation between AD stage and activation of pro-ceramide genes, ceramide levels and molecular indices of endoplasmic reticular stress in postmortem human brain tissue. The correlation was established when considering brain insulin/Insulin growth factor (IGF) resistance. To add insult to injury, the study also noted that insulin/IGF resistance was further propagated by the dysregulation of ceramide, implying a positive feedback loop once some resistance has already been established.
To date, I have never heard or even considered the linkages between brain dysfunction and insulin resistance albeit a very intuitive phenomenon. What this tells me is that a state of metabolic syndrome or prediabetes, which afflict so many people today, could actually cause neurodegeneration and dysfunction, a lot earlier on than we’ve thought. Could the high prevalence of Alzheimer’s disease today, that was once written off as caused by the prolongation of life that is so common to contemporary living, can be actually caused by our poor diet and exercise habits, once again? At first glance, many younger people may not care vary much about Alzheimer’s disease, as it is a disease, typically, of older age, however once one considers the fact that AD is a continuum of disease and not a pathology that produces itself spontaneously, a more prudent outlook may render necessary. What may be found later on, is that if losing proper sugar metabolism harms your brain, would keeping your blood sugar tight make your smarter/keep you smart?