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