Alzheimer\'s: The Unsolved Mystery





























Absentmindedness, with questions having to be repeated, trouble following conversations, or remembering people\'s names, sound familiar? These are classic early stage symptoms of Alzheimer\'s.
Alzheimer\'s is a type of dementia in which parts of the brain stop working, causing memory loss, and instability in judgement, reasoning and emotions. Dementia, such as Alzheimer\'s is usually more frequent in elderly people. Approximately 15 percent of people who are over 65 will develop some form of dementia; by the age of 85 that percentage increases by at least 35 percent. Alzheimer\'s is the most common dementia, nearly four million Americans suffer from it.
Alzheimer\'s is a very complex disease. So complex that very little has been discovered about it but that is rapidly changing. Findings from epidemiology, genetics, molecular and cell biology are fitting together in the Alzheimer\'s puzzle, helping researchers to identify some of the mechanisms that underlie it. Alzheimer\'s starts because the normal processing of certain proteins goes terribly wrong. This causes brain cells and the spaces between them to be cluttered with pieces of toxic protein. Closer investigating with microscopes has revealed a loss of nerve cells in certain regions of the brain. Some of these dying nerve cells communicate using the neurotransmitter acetylcholine, these compounds eventually break down by an enzyme called acetylcholinesterase. Also responsible for Alzheimer\'s are clusters of proteins in the brain which come in two forms: those found inside the nerve cells and those found in between the cells.
The clusters inside the cells look like pairs of threads wound around each other in a helix. The tangles consist of a protein called tau. Tau binds to another protein called tubulin. Tubulin then forms structures called microtubules which run through cells, giving support and shape. Also the microtubules provide pathways for nutrients and other molecules to travel through.
The main problem is that researchers can\'t quite figure out how Alzheimer\'s is started. Some the leads are its inherited genetically, is caused by major head injury, poor early childhood education and exposure to aluminum in drinking water.
Amyloid plaques are the second kind of protein deposits in the brain. These deposits gather in the spaces between the nerve cells, causing the neurons to look swollen and mutated. The clusters of protein usually accompanied by reactive inflammatory cells, which might degrade and remove damaged neurons. These plaques are specific to Alzheimer\'s patients and appear long before the tangles do. The main component of these plaques are peptides made up of 40-42 amino acids, the BAPP protein. However BAPP remains a mystery. Researchers know that many different cells produce BAPP and that it be in between 695-770 amino acids long. The protein runs through the outer membrane with a short piece cutting into the cell and a longer piece sticking into the extracellular space. The B-amyloid peptide is cut out of the section of BAPP that spans the cell membrane. Scientists discovered that BAPP is cut in two different ways. One way the proteins is first cleaved by an enzyme called alpha-secretase. Then it is cut by another putative enzyme, gamma-secretase. This sequence of cuts creates a harmless peptide fragment.
The second way BAPP is clipped by beta-secretase. One of the resulting pieces C99-BAPP is then snipped by gamma-secretase and the B-amyloid peptide is born, some of which may have two extra amino acids. This slightly longer form is the one that gives rise to plaques and that it has a direct toxic effect on neurons. First, the peptide seems to disrupt calcium regulation which can cause cell death. Second, it may damage mitochondria causing the release of free oxygen radicals which then damage proteins, lipids, and DNA. Finally, it may bring about the release of cellular compounds.
Researchers discovered mutations in a set of genes that interfere with the cutting of BAPP. These disruptions are located on the 1 and 14 chromosomes and cause a very aggressive early stage of Alzheimer\'s. These findings helped support the BAPP theory for Alzheimer\'s. The disruptions cause gamma-secretase to be cut many more times than usual and an overproduction of B-amyloid peptide is made.
I believe that scientists have just now uncovered the tip of the tree with the disease of Alzheimer\'s. More research needs to be done on this amazingly complex disease. The BAPP theory only accounts for five percent of all Alzheimer\'s cases. Some may believe that this is a small step in uncovering the mystery of Alzheimer\'s but I believe it will be a huge one after its throughly examined. The BAPP discovery should help open the door for Alzheimer\'s and reveal more about how the disease functions and what exactly causes it. For those people who are infected with the disease they can only sit in agony and hope that a more powerful insight is made for the sake of future generations. It is believed that by 2025 more than 22 million people world wide will be infected with Alzheimer\'s and as the average life span lengthens the percentage only gets steeper.
Alzheimer\'s is the worst kind of disease. It not only infects the being with which it is in but it also affects the people who know and love that person. For mankind\'s sake hopefully more work will be put into establishing a cure for this awful dementia.




Bibliography:
Author: Peter H. ST. George-Hyslop , Scientific American, December 2000