makes a person forgetful and as
the condition progresses, it affects other mental functions as well. There are
several drugs that are available for its treatment. However, these drugs can
only slow the progression of Alzheimer's disease but cannot cure it. They are
mostly effective in early stages of Alzheimer's disease. In late stage
Alzheimer's, the affected individual is usually completely dependent on the
Drugs that are currently used in Alzheimer's disease affect
neurotransmission, that is, the signalling between nerves. When information
from one nerve has to be passed to another, a substance called a
neurotransmitter is released from the first nerve which docks on the next nerve
and conveys the signal. Since neurotransmission via acetylcholine is reduced in
Alzheimer's disease, drugs that enhance this neurotransmission which include
, donepezil and
rivastigmine are beneficial in the treatment of Alzheimer's disease. Another
drug memantine acts via another signalling pathway called the glutamate
Several other drugs which affect neurotransmission are also
being evaluated for the treatment of Alzheimer's disease. But that is not all.
New strategies are being explored which would hopefully lead to the development
of drugs that could even cure Alzheimer's disease. The review article by Justin
Davis and Robin Couch highlights just this, and is summarised below.
Drugs for Alzheimer's disease under investigation act
through several mechanisms which include the following:
Inhibition of the Enzymes β Secretase and ɣ Secretase
Patients with Alzheimer's disease have accumulations of
amyloid-β peptides in the brain. These are generated from another protein
through the action of two enzymes β secretase and ɣ secretase. Thus, drugs that
inhibit these enzymes could possibly prevent the accumulation of amyloid-β
peptides in the brain and play a role in the treatment of Alzheimer's disease.
However, drugs that completely inhibited ɣ secretase were
associated with serious side effects and could not be developed as
Therefore, drugs that bring about modulation of ɣ secretase instead of complete
inhibition are being evaluated instead. Inhibitors of β secretase have
comparatively fared better in clinical trials. However, one of these drugs
turned out to be toxic to the liver and its development had to be discontinued.
Vaccination against Alzheimer's Disease
Another approach to develop treatment for Alzheimer's
disease is by vaccination. A vaccine introduces some components of the β
amyloid peptide into the body which is likely to stimulate the body to produce
antibodies. These antibodies will probably act against the β amyloid deposits
in the brain, and hopefully cure the disease. It is necessary to develop a
product that does not produce brain inflammation, and thereby result in further
Instead of a vaccine that produces antibody response, it
has been suggested that direct injection of antibodies that will act against
the β amyloid protein, may be an effective treatment. However, current research
using this approach has yet to yield successful results.
Inhibition of Hyperphosphorylation of tau
Another important pathology seen in Alzheimer's disease is
the formation of neurofibrillary tangles in the brain. These are composed of a
hyperphosphorylated form of a protein called tau. Normal tau associates with
microtubules, which play an important role in the structure and function of the
nerves, while hyperphosphorylated tau contributes to neurofibrillary tangles
and deposits in nerves. Hyperphosphorylation is mediated by several enzymes
called kinases. This has encouraged research in developing:
of kinases, which would prevent hyperphosphoryation of tau and thereby allow
normal functioning of tau. Inhibition of these enzymes could result in some
other unknown benefits as well.
- Inhibitors of tau aggregation.
Drugs that stabilize microtubules and thereby restore the
structure and function of neurons could also be beneficial.
Other Treatments that are also being investigated
to reduce oxidative stress and prevent
damage to nerves.
- Drugs to induce ketosis, so that the
brain can use ketones as a source of energy instead of glucose. There are
problems in using glucose by the brain in patients with Alzheimer's disease. Therefore, alternate sources of energy may be
beneficial. Medications providing medium chain fatty acid has also been tried
- Drugs that suppress inflammation, since inflammation
may be a part of Alzheimer's disease.
- Drugs that reduce
neurodegeneration. In Alzheimer's disease, certain neurons get destroyed. Neurotrophins
are substances that promote growth and survival of neurons. Studies are
therefore directed towards finding methods to deliver neurotrophins to the
brain, or to increase the production of neurotrophins by the body. Certain
phosphodiesterase inhibitors ultimately increase the level of neurotrophins and
therefore are being investigated for the treatment of Alzheimer's disease.
that act on several other targets that include HMG-CoA reductase, peroxisomes,
angiotensin receptors, heparanase matrix metalloproteinase, hormone
supplementation and vitamin supplementation.
The diverse approaches to developing drugs for Alzheimer's
disease will hopefully culminate into at least a few drugs to cure this
Davis, J. and Couch, R. (2014) Strategizing the Development
of Alzheimer's Therapeutics. Advances in Alzheimer's disease, 3,
107-127. doi: 10.4236/aad.2014.33011.