Alzheimer’s Disease (AD) remains as one of the most fearful diseases for mankind today. There are not many treatments known, and the impacts that this disease has on the patient, families, and friends of patients are extremely difficult to bear. Although there is no cure at this point, scientists have been working to understand more about the disease and attempt to find a cure sometime in the future.
This disease is considered as the most common form of dementia, affecting about 60 percents to 80 percents of the cases for elderly. The early stage of AD is characterized by “an impairment of recent memory function and attention, followed by failure of language skills, visual-spatial orientation, abstract thinking, and judgment.”1 It is clearly a terrifying disease, influencing basically every single part of a person’s life.
Biological Mechanisms Behind AD
When we think about someone who becomes ill, we try to understand why. For AD, a popular theory points the finger to a protein fragment named amyloid-beta 1-42.2 This protein fragment’s hazardous interaction with a particular ion channels in the outer membrane of neurons has been frequently mentioned as one of the critical factors to the development of AD. The result of this interaction is the unusual flow of Ca2+ ions into the cell, which eventually lead to the deaths of the cells. Once these brain cells die, they cannot be replenished, creating a permanent problem.
Now, let’s delve deeper into the enigma of this fragment. Although there are different arrays of circumstances involving AD, they all point that a “misfolded” fragment of amyloid precursor protein (APP) is the source of amyloid-beta 1-42. Such misfolding occurs because of unusual cutting or cleaving of the protein than the norm. In normal cases, APP becomes cut at three sites by three proteases, or protein-cutting enzymes – alpha, beta, and gamma-secretase. Beta-secretase is actually pictured in this article as well. But, in the unusual situation for development of AD, beta and gamma-secretase become much more active with reduced activity for alpha-secretase, leading to different sizes of protein fragments than usual. The reasons as to why this different level of activity occurs are not clear at this point.
The produced protein fragments are usually in length of 39 to 43 amino acids, and amyloid-beta 1-42 is the most toxic form of the resulted fragments. So, why are these fragments toxic? They become toxic because when these fragments become aggregates, they interfere with a particular channel and lead to an increased amount of Ca2+ into the cell than usual.
“All neurotransmitter release appears to be Ca2+ dependent. Depolarization of the presynaptic membrane opens voltage-gated Ca2+ channels, allowing Ca2+ to enter and trigger neurotransmitter release.”3 When there are too much Ca2+ ions coming into the cell, this translates into too much stimuli, and as a result, the information will not be delivered well – clearly reflecting the inabilities of patients to carry out everyday tasks. Eventually, these aggregates will lead to the cell deaths known as apoptosis.
AD is particularly related to Down Syndrome as well. People with Down Syndrome has an extra chromosome 21, and they are likely to develop AD earlier than other people. This is because chromosome 21 codes for APP, so an extra chromosome 21 will lead to an increased amount of amyloid proteins in the person’s body. Also, one cannot help wonder on why older people are more affected by AD. One theory is that as one ages, one has less energy, or ATP (adenosine triphosphate), to defend itself against amyloid-beta 1-42.
There are already drugs like Aricept, Cognex, and Exelon out in the market to aid patients with AD. The three drugs try to alleviate the impacts of AD by inhibiting the enzyme acetylcholinesterase to raise the level of acetylcholine, an important neurotransmitter in the human body.
Furthermore, Vernon M. Ingram, the author of American Scientist article cited in this article, stated that he and his colleagues did several researches to add a small molecule to amyloid-beta 1-42 and change its structure to be nontoxic. There are, however, still a lot of works to be done regarding this method.
Future of Alzheimer’s Disease
As I explained in this article, amount of information that scientists has gathered about AD is constantly increasing. Compared to how this disease could not be diagnosed until the autopsy after the death (how useful is that diagnosis?), there has been a clear increase in amount of information we know about AD. Though there is no cure at this point, we can try to be optimistic that given how much information we now know about mechanisms affecting AD, there will hopefully be a drug that can inhibit the development of AD without causing major side effects to its patients in the near future.
1 Dale Purves et al., Neuroscience, 3rd Edition (Sinauer Associates, Inc., 2004) 750.
2 Vernon M. Ingram, “Alzheimer’s Disease,” American Scientist July-August 2003 Vol. 91, No. 4.
3 Richard W. Hill, et al., Animal Physiology (Sunderland: Sinauer Associates, Inc., 2004) 324.
Note: Unless stated otherwise, majority of the scientific information in this article came from the American Scientist article cited in #2.