Alzheimer's Disease is Type 3 Diabetes?

Alzheimer’s Disease (AD) is the most common type of dementia. It is a long-term disease characterized by the progressive loss of memory and cognitive functions. What begins as mild memory loss eventually leads to the inability to learn new information, long-term memory loss, cognitive impairment, and even depression and irritability.

So what causes AD? Without getting into the details, patients typically have decreased brain mass, amyloid‐beta (Aβ) plaques, tau tangles, chronic oxidative stress, impaired energy metabolism, activation of pro-apoptosis pathways, the list of symptoms goes on and on. Current therapies include cholinergic targets, NMDA receptor antagonists, anti-inflammatory agents, and more novel treatments for inhibiting the buildup of these plaques and tangles, none of these therapies prove to be a definitive treatment for AD.

So how does our brain accumulate so much damage? And what do all these symptoms have in common?

Steen et. al. in 2005 discovered something interesting about our brain, not only does our pancreas produce insulin, our brain also produces it’s own insulin and insulin receptors. More importantly, CNS in AD patients has markedly lower levels of both insulin and insulin receptors, leading to lowered expression of downstream pathways needed to maintain proper cell functioning. This has led some scientists to think about Alzheimer’s disease as a metabolic disease, and thus coining the term – Type 3 Diabetes.

So how far-fetched is this idea? AD is now a type of Diabetes? Actually, experiments show support for this hypothesis. AD animal models injected intracerebrally with anti-diabetic drugs (PPAR-δ agonist), showed significant improvements in learning and spatial-memory tasks. Not only that, well… read the following results from a review by de la Monte et. al.

“ …the PPAR agonists rescued the ic-STZ model by lowering critical AD associated indices of oxidative stress, including microglial and astrocyte activation, p53, nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase gene expression, lipid peroxidation, DNA damage, APP expression, and tau phosphorylation."

All this was accomplished by just manipulating the level of insulin and insulin receptors in the brain. That was in 2008. Today, better drugs such as GLP-1 is being developed in order to cross the BBB and affect the desired target sites. Hopefully thinking about AD as a metabolic disease is the key to finding an affective cure for this debilitating disease.