Disease from Age or Age from Disease? What is Alzheimer’s Disease?

Alzheimer’s Disease (AD) is the leading cause of dementia and is estimated to affect 36 million people worldwide.  There are cases of early-onset AD, however it is very rare, occurring in less than one percent of all instances.  Although there are genetic components associated with being predisposed to AD, it is primarily a disease of aging.  Several common symptoms that are associated with AD are, memory loss, confusion, irritability, aggression, mood swings, and loss of articulation.  The current prognosis for someone who is diagnosed with AD is seven years.  The drugs that are currently approved for AD only treat symptoms and not the disease itself.  However there are many treatments that are currently being tested.  But before we delve into these new treatment options, we must first examine the pathway by with AD operates.

Pathways
PI3-K/Akt:
The PI3-K/Akt (phosphoinositide 3-kinase)/Akt is a signaling pathway which is primarily activated by insulin and IGF-1 (insulin-like growth factor-1).  Besides having a name filled with confusing acronyms, the PI3-K/Akt pathway that is found at high levels in the brain.  The pathway begins when the signaling molecule (insulin) binds to the membrane receptor (which is a receptor tyrosine kinase RTK).  This then leads to a cascade of phosphorilation (changing the conformations of proteins down stream) which ultimately leads to cellular responses such as survival, metabolism, growth, repair, etc.  Several key regulatory proteins that are found in the cycle are mTOR, GSK3ß, and FOXO.
Tau
Tau is an important protein which is found farther down the pathway of PI3-K/Akt.  It is regulated primarily by mTOR in particular and contributes to one of the primary causes of AD — neurofibrillary tangles (NFT) — when unregulated.  In addition, this pathway is further expressed when there are elevated levels of Aß plaques, another primary cause of AD.  Not surprisingly, it is a vicious cycle, the more Aß plaques, the more NFTs.  The question then remains, what can be done to regulate and control these pathways and reduce the affect of AD?

Treatment options
Acetylcholinesterase inhibitors & NMDA receptor antagonists
Acetylcholinesterase inhibitors and NMDA receptor antagonists are the current methods of AD treatment.  While effective, these treatments do not last very long and AD continues down its disastrous course.  Because of this, many new options of treatment are being examined.
Intranasal insulin therapy
Clinical trials of intranasal insulin therapy have been tested on patients who are beginning to show signs of cognitive decline.  This treatment targets the central nervous system (CNS) but not the periphery.  Initial trials have been showing promise.
Aß Inhibitors
Additional clinical trials are being conducted which target and reduce the levels of Aß in the brain.  Drugs such as GLP-1, exendin-4, and liraglutide treat deficits in insulin signaling which is directly connected to elevated levels of Aß plaques.
PI3-K/Akt pathway regulation (calorie restriction)
Much like most functional problems in the body, there is a medical pharmaceutical solution to the issue, and then there are lifestyle and dietary solutions.  In the case of the PI3-K/Akt pathway, practicing caloric restriction keeps the system in balance even with age, and therefore prevents against the progression of AD.