The two hallmarks of Alzheimer's disease (AD) are amyloid plaque deposition and hyperphosphorylated tau-mediated tangle formation. While inhibitors of these processes are now being studied in the clinic, currently available therapies such as cholinesterase inhibitors and the NMDA antagonist memantine only treat symptoms of AD. A less-studied aspect of AD etiology involves insulin dysregulation in the brain.

Recent studies of postmortem brains from AD patients suggest that sporadic AD may result from a cascade involving dysregulated neuronal insulin signaling systems. This cascade is associated with generation of reactive oxygen and nitrogen species, mitochondrial dysfunction and cholinergic neuronal degeneration, in addition to plaque and tangle formation. Whether AD is type 3 diabetes, unique to the brain, or whether diabetes is a risk factor for AD remains to be elucidated. Understanding the connection between insulin function and AD might enable discovery of a drug-combination that prevents, delays, or halts progression of sporadic AD.