For many years I have been following the clues connecting Alzheimer’s Disease to diabetes because I am a diabetes specialist and I have experienced the loss of a love one who acquired Alzheimer’s disease at an early age. I have just found startling evidence that insulin has a major role in the brain, and I will share with you the evidence that is mind boggling to me.
Only a few years ago it was assumed that the brain was “insulin insensitive” because glucose can be taken up in brain cells, without the involvement of insulin or insulin receptors. However studies in recent years have shown that insulin plays a significant role in the brain.
It has been said that people with diabetes have a 70% higher risk of getting Alzheimer’s Disease. Research shows that levels of brain insulin and its related receptors are disrupted in people that suffer from Diabetes, and in people suffering from Alzheimer they found diminished insulin receptor signaling.
Can Insulin Protect Brain Against Alzheimer's Disease????Quite possibly, yes. Recent research suggests that Alzheimer's disease is akin to diabetes of the brain and therapies for diabetes may be useful for both. It is now theorized that in Alzheimer's, the aging brain can develop insulin resistance or suffer from a dwindling insulin supply, damaging neurons and contributing to the widespread destruction of the brain.
I will now give a synopsis of what I consider the most important findings to support this theory:
1. Researchers from Northwestern University, Evanston, Illinois and Universidade Federal do Rio de Janeiro in Brazil published a study on Feb 2, 2009 in Proceedings of the National Academy of Sciences.
“I think a role of insulin in the brain is to defend against insult,” says William Klein, a neuroscientist at Northwestern University in Chicago. “We've been thinking of the root cause, since 1906, as plaques and tangles – but what causes those?” Dr. Klein has investigated insulin's role in Alzheimer's for more than a decade, and he believes a shortage of insulin contributes to the build-up of amyloid plaque, which in effect unites the competing theories. He also has diabetes himself, and says “I can tell you that too little or too much insulin leads to confusion.”
Dr Klein also notes that the hippocampus, the brain's key memory region is notoriously vulnerable to Alzheimer's Disease. The hippocampus has a widespread network of insulin receptors and that insulin not only helps neurons communicate, it clears waste products that can jam brain function.
Scientists at Northwestern University discovered toxic proteins called Aβ-derived diffusible ligands (ADDLs) that attach themselves to specific sites on synapses (the junctions between brain cells that are important for memory formation) and stop the synapses from relaying messages between brain cells. This is a characteristic symptom of Alzheimer's disease.
Scientists from Northwestern University in the USA and Universidade Federal do Rio de Janeiro in Brazil discovered that insulin may slow or prevent the damage and loss of memory of Alzheimer’s Disease by blocking the action of toxic proteins that attack brain cells. This adds more evidence that Alzheimer'sDisease may actually be a third type of diabetes caused by weakening of insulin signaling in the brain.
2. September 23,2010 reported in The Globe and Mail:”Insulin may hold key to ‘Diabetes of the brain”
In this study the researchers showed that treating brain cells with insulin and Avanti effectively stopped the ADDL proteins from attaching themselves to the cells. They also showed that Avanti enhanced the protective effect of even low levels of insulin. The insulin reduced the number of binding sites by which the ADDL proteins could attach themselves to the synapses.
They used cultures of neurons taken from the hippocampus, and treated them with insulin and Avandia. Cells in the hippocampus are particularly vulnerable to damage by ADDL proteins.
Senior author William L Klein, a professor of neurobiology and physiology in the Weinberg College of Arts and Sciences who also does research at Northwestern's Cognitive Neurology and Alzheimer's Disease Center, said in a statement that drugs to enhance insulin sensitivity in the brain could open up new treatments for Alzheimer's.
The researchers concluded that:"The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD [Alzheimer's Disease] pathogenesis."
In 1994, Dr. de la Monte published a paper declaring Alzheimer's to be “Type 3 diabetes.” She has found that insulin helps brain cells talk to one another, that nerve fibres stretching between them are “studded with insulin receptors” and that insulin is crucial to memory and learning. At first, she says, her work received little attention because it did not jibe with the plaque-as-key-perpetrator hypothesis: “I would never say amyloid has no role, but it may have a role if something else is already wrong.”
In the 1980s, neuropathologist Patrick McGeer, now professor emeritus at the University of British Columbia, also found that Alzheimer's and diabetes have common features. His team discovered that people with diabetes have inflammation and amyloid plaque build-up in the pancreas, just as people with Alzheimer's have in their brains. But he is not convinced that insulin drives the disease. “It's peripheral,” he says, adding that an insulin treatment for Alzheimer's could be dangerous since too much insulin in the brain “would be toxic.”
v Recently, when GlaxoSmithKline tried its controversial drug Avandia as a treatment for Alzheimer's, the company concluded it was no better than standard treatment and halted development. Dr. de la Monte (the physician who first identified Alzheimer’s Disease as Type 3 Diabetes )however, felt the test subjects did improve, but that the doses they were being given were too high. Others, such as Dr. Klein at Northwestern, say that Avandia, as with most failed Alzheimer's therapies, was given too late in the disease to make a difference.
v Autopsy studies show that Alzheimer's patients have low levels of insulin in the brain, which University of Kansas researchers suggest is related to brain damage and poor cognition – and contribute to tau, the protein behind the nerve tangles common in the disease.
v At an International Alzheimer's Conference (2019) held in Honolulu, University of Washington researchers presented results of a small study that found that people treated with an insulin-based nasal spray showed memory improvements, and no signs of serious side-effects. In that study,109 people in the early throes of Alzheimer's disease squirted insulin up their noses for four months.
European Journal of PharmacologyVolume 490, Issues 1-3, 19 April 2004,”The brain has long been viewed as an insulin-insensitive organ. Following the demonstration of insulin receptors in the brain, this assumption has been challenged, and a whole new field of research has emerged. Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signaling and glucose homeostasis are implicated in brain pathology. “
Diabetes. 2011;60(2):443-447. © 2011 American Diabetes Association, Inc Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose ToleranceJussi Hirvonen; Kirsi A. Virtanen; Lauri Nummenmaa; Jarna C. Hannukainen; Miikka-Juhani Honka; Marco Bucci; Sergey V. Nesterov; Riitta Parkkola; Juha Rinne; Patricia Iozzo; Pirjo Nuutila
Friday’s Globe and Mail on web: Sept 23, 2010 Insulin may hold key to “diabetes of the brain”
Pharmacology. Volume, 19 April 2004, Pages 1-4
Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease Authors:Geert Jan Biessels (Department of Neurology, , Rudolf Magnus Institute of Neuroscience, University Medical Centre), Bert Bravenboer (Department of Internal Medicine, Catharina Hospital, Eindhoven, The Netherlands) and Willem Hendrik Gispen (Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands ) Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands.