Alzheimer's Disease is Type 3 Diabetes: Evidence from Human Studies

This hypothesis was directly investigated by first examining postmortem cases of advanced AD and determining if the neurodegeneration was associated with significant abnormalities in the expression of genes encoding insulin, IGF-1, and IGF-2 peptides, their receptors, and downstream signaling mechanisms.5 In that study, we demonstrated advanced AD to be associated with strikingly reduced levels of insulin and IGF-1 polypeptide and receptor genes in the brain (Figure 1). In addition, all the signaling pathways that mediate insulin and IGF-1-stimulated neuronal survival, tau expression, energy metabolism, and mitochondrial function were perturbed in AD. This study carries additional significance because it established that, like all other pancreatic and intestinal polypeptide genes, the insulin gene was also expressed in the adult human brain. Moreover, the results taught us that endogenous brain deficiencies in insulin, IGF-1, IGF-2, and their corresponding receptors, in the absence of T2DM or obesity, could be linked to the most common form of dementia-associated neurodegeneration in the Western hemisphere. Since the abnormalities identified in the brain were quite similar to the effects of T1DM or T2DM (though none of the patients had either of these diseases), including abnormalities in IGFs,81–83 which are important for islet cell function,84,85 we proposed the concept that AD may represent a brain-specific form of diabetes mellitus and coined the term “type 3 diabetes.”

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/