Alzheimer Disease (AD) and a host of other so-called neurodegenerative diseases such as Parkinson Disease and Lou Gehrig Disease (also called ALS -- for Amyotrophic Lateral Sclerosis -- a wasting disease that tends to affect motor nerves and secondarily muscle function in the arms and legs as well as the swallowing and breathing muscles) have been refractory to treatment largely because the exact cause of each of these devastating disorders is unknown. They have been the subject of intense research to no avail -- that is until recently. A remarkable paper was recently published in the medical journal Neuron. The lead author was Dr. Robert Vassar from Northwestern.

The purportedly toxic compound that builds up in the brains of persons afflicted with AD is called beta-amyloid (A-beta for short). It is produced by the cleavage of amyloid-beta precursor protein (APP) by the action of beta-site APP cleaving enzyme 1 (BACE1). This accelerates the buildup of A-beta. The level and activity of BACE1 are increased in the brains of AD patients. This led to the idea that the chronic increase in BACE1 in the brain may contribute to the development of AD.

This is not of much help to those persons at risk for this devastating disease unless something can be done about it. From a pharmaceutical perspective, such hope is on a distant horizon. However, an interesting observation might provide a clue as to what leads these sticky amyloid fibrils to form and aggregate. This insight was identified by the application of several metabolic manipulations that each decreased energy generation in neurons. One involved impairing the electron chain, which is the main conveyor belt that turns food into energy. Another was a potent inhibitor of an enzyme in the glucose metabolic pathway, while yet another manipulation involved administering an overdose of insulin to the lab animal. This latter model of energy impairment caused cerebral brownouts by causing blood glucose levels to fall to markedly subnormal levels. This prevented the neurons from accessing their primary fuel -- glucose.

The common thread in each of these models was an increase in BACE1 and the accumulation of A-beta.

The researchers suggested that physiologic changes that increased blood flow to the brain, which would deliver more oxygen and more glucose, would enhance energy production and lessen A-beta via a beneficial effect on BACE1. What they omitted to mention is that many neuroscientists are starting to refer to AD as Type 3 diabetes because of the presence of a similar inability of the brain to take up and metabolize glucose as that which exits in the tissues of the body in Type 2 diabetes (the type generally associated with obesity). This is significant because diabetes is a metabolic disorder that responds to various lifestyle factors that stabilize blood sugar swings and enhance insulin sensitivity. These same interventions would be expected to enhance cerebral glucose metabolism and act to alleviate energy shortages, BACE1 activation and accumulation of A-beta, the alleged culprit behind the initiation of AD.

These findings are consistent with a reversible etiology of one of the primary modern day medical scourges. One that we may ameliorate by making appropriate lifestyle choices that are easily within our control.