Emerging research reveals that stored glucose and brain-produced insulin may be key players in the progression of neurodegenerative diseases like Alzheimer's. These findings open the door to potential therapies that go beyond amyloid plaques and tau proteins - the hallmarks of the disease.
- Tau protein and glycogen accumulation in the brain of Alzheimer’s patients
- Insulin produced in the brain
- Diet, drugs and new strategies to manage brain glucose and insulin
- Brain insulin and cognitive aging - what’s next
Tau protein and glycogen accumulation in the brain of Alzheimer’s patients
In a breakthrough led by the Buck Institute for Research on Aging, scientists showed that glycogen accumulation in the brain is closely tied to tauopathies, particularly Alzheimer’s disease. Tauopathies are neurodegenerative diseases marked by the accumulation of tau protein inside nerve cells. Previously, glycogen was considered biologically passive in the brain, used only as an emergency energy reserve. This study proved otherwise: glycogen interacts directly with tau, contributing to neuron degeneration.
Using fruit flies as a model, researchers observed that tau disrupted the normal metabolism of glycogen. Instead of being broken down into usable energy, glycogen built up, further increasing the toxic load in neurons. Human brain samples from Alzheimer's patients confirmed this pattern. When the main glycogen-processing enzyme, glycogen phosphorylase (GlyP), was enhanced in the flies, cell damage was reduced and their lifespan extended. This showed that metabolic dysfunction in Alzheimer’s might be more influential than previously thought.
Insulin produced in the brain
Since 1978, scattered studies hinted that insulin existed in the brain. But these findings were dismissed for years. Newer research confirms that brain cells do, in fact, produce insulin - independently of the pancreas. Multiple brain regions were found to harbor insulin-producing cells, including the hippocampus, hypothalamus, olfactory bulb and the choroid plexus. Each area plays different roles in memory, appetite regulation, and stress responses.
For instance, insulin-producing neurogliaform cells in the hippocampus react to glucose levels similarly to pancreatic beta cells. In the hypothalamus, which controls metabolism and growth, insulin was found to be directly related to the production of growth hormone. When these insulin levels dropped due to stress in lab mice, the animals showed stunted growth. This supports the idea that brain-derived insulin is crucial for long-term neurological and physiological health.
Diet, drugs and new strategies to manage brain glucose and insulin
One of the most promising findings involved dietary intervention. Flies with tauopathy that were fed a low-protein diet lived longer and showed reduced neuronal damage. The metabolic changes caused by restricted diets appeared to boost GlyP activity, helping neurons handle stress more effectively. To simulate this effect, scientists used a molecule called 8-Br-cAMP. The results were nearly identical - less damage, longer lifespan.
Additionally, the researchers drew attention to diabetes drugs like Ozempic, known for targeting GLP-1 receptors. These medications may indirectly improve brain health by influencing how glycogen is processed. If GLP-1 pathway modulation can reduce tau build-up or improve insulin sensitivity in the brain, they might be repurposed for dementia treatment. While this connection is still under investigation, it aligns with other findings showing that insulin resistance in the brain - often seen in Alzheimer’s - may mimic Type 2 diabetes.
Brain insulin and cognitive aging - what’s next
Although brain insulin doesn’t regulate blood sugar like its pancreatic counterpart, its role in neurological health is increasingly evident. In Alzheimer’s patients, where insulin resistance in the brain leads to a 20% energy gap, this deficiency impairs cognitive function long before cells die. Some studies show that intranasal insulin - sprayed into the nose - improves memory and delays symptoms in early Alzheimer’s.
However, more is not always better. In women, higher insulin levels in cerebrospinal fluid have been associated with worse memory performance. This highlights the complexity of brain metabolism and the need for precise regulation. It also raises new questions: did the brain or the pancreas evolve first to produce insulin? What are the long-term consequences of manipulating these pathways?
As research progresses, one message is clear: understanding how the brain manages glucose and insulin is critical to addressing age-related decline. With growing evidence and advanced tools, scientists are finally unlocking mechanisms that may revolutionize treatments for Alzheimer’s and other neurological conditions.
Source: Science Alert