Pathology: called amyloid precursor protein or APP. Not

Pathology: How Alzheimer’s disease effects the brain

55,000 people in Ireland are affected by Alzheimer’s, a figure which is growing every day. Because this disease is so prominent in our society
it is important for us, as chemists, to not only be aware of the facts and
statistics, but also what chemical reaction and imbalances make this disease as
devastating and fast acting as it is. In people diagnosed with dementia and
Alzheimer’s the cerebral cortex is damaged and shrivels up. This is
the outer layer of the brain and plays a key role in memory, attention,
perception, cognition, awareness, thought, language, and consciousness. This
Shrinkage is especially severe in the hippocampus, an area of the cortex that
plays a key role in formation of new memories.
Also evident from the picture is a growth in the size of the brain’s
ventricles. These are fluid filled spaces within the brain and as they grow
they further compress the cortex which further contributes to tissue loss
within the brain. But what causes this to happen? (National institute of aging, n.d.)








Amyloid, which are peptides of amino acids, are crucially involved in
Alzheimer’s disease. Beta-amyloid is a section of a larger protein which
is called amyloid precursor protein or APP. Not much is actually known what service
this amyloid precursor proteins actually does but from research scientists know
a great deal about how it appears to function. In its complete form, APP
extends from the inside to outside of the brain cell by passing through the membrane
around the cell. When APP is “activated” to do its normal job, it is cut by
other proteins called Alpha secretase and Gamma secretase into separate,
smaller sections that stay inside and outside cells. There are several
different ways APP can be cut by different enzymes. When cut by two certain
enzymes in a certain place, the fragment produced is beta-amyloid.












plaques form when certain proteins within the cell of the neuron are processed
differently. Normally, the previously mentioned enzyme alpha-secretase cuts the
APP, which releases a fragment while another enzyme, Gamma secretase, also cuts
the protein in a different place. These fragments are thought to benefit
neurons. However, in the cells of an Alzheimer’s patient, the first snip of the
protein is made usually by another enzyme Beta secretase. This enzyme plays a
crucial role in the formation of sleeves of fatty tissues called myelin sheaths
which encase the nerve cells protecting it from viruses and disease. (Alzheimers
universal, 2010)
When Beta secretase cleaves the APP, combined with the cut made by gamma
secretase, this results in the release of short fragments called beta amyloid. (webmd, n.d.) Beta amyloid
fragments then come together and become insoluble eventually forming clumps and
plaques. (Cognitive disorders, n.d.)









leading cause of Alzheimer’s are neurofibrillary tangles. These are created
when a protein called Tau is modified. In normal brain cells, these proteins are
crucial in the structural integrity of the cells internal transport system.
Nutrients and other cellular cargo are carried up and down structures called
microtubules to all parts of the neuron. In Alzheimer’s patients, abnormal Tau
separates from the microtubules causing them to fall apart. Strands of this
then dislodged Tau clump together and become
insoluble to form tangles inside the neuron which can block the transport system.
(Bailly, n.d.)The furthest away nerve endings from the
nucleus of the cell, which are at the end of the axon, are the first
microtubules to disintegrate. As time goes on the destruction travels up the
axon moving closer to the nucleus. (Alzheimers universal, 2010) As a result, communication
between the nerve endings and the cell brain is reduced and, once the
entire neuron has degenerated, cut off completely. (Alzheimer’s
Universal, n.d.)








There are
other cells within the brain which are tasked with clearing debris and other
unwanted particles. These cells are called astrocyte and microglia. As the
microglia cells attempt to clear away the plaques created by the beta amyloid,
they are overwhelmed and chronic inflammation sets in. (Alzheimers universal, 2010)The astrocyte then
react to the overwhelmed microglia but the damage is already done. With these
defence cells disabled, Neurons eventually lose their ability to transport
nutrients and information to each other and become dethatched and die. (national institute of aging, 2017)As time goes on,
plaques and tangles effect millions of neurons which begin to breakup and die.
It is this mass wipe-out of neurons that leads to the aforementioned tissue
loss within the brains cerebral cortex, and more precisely, the hippocampus.

contributing factors

Years of research has pointed towards
neurofibrillary tangles and beta-amyloid plaques being the two main
contributing factors in the formation of Alzheimer’s disease, however, there
are several other reasons responsible. (Roskey, n.d.)


Other than
beta-amyloid and the tau protein, Neuroinflammation is the third most prominent
contributing factor in Alzheimer’s disease. When the APP’s are cut, they tend
to deposit in the A? plaques. The APP
protein previously mentioned, is released within the brain following a
concussion or other trauma. The effects of neuroinflammation are controlled by
microglial cells which are a potent generator of free radicals. Studies have
revealed a number of abnormalities in the microglial cells reaction to Alzheimer’s
disease. These abnormalities are triggered by Beta-amyloid and tau and in turn
help them to spread throughout the brain. (Neuropthology, 2016)



As the brain ages,
it is put der stress by oxidation which in turn causes small mitochondrial DNA
mutations. This process is speeded up in patients with Alzheimer’s disease by
the presence of Beta-amyloid plaques and the previously mentioned microglia (Neuropthology,


Because of low levels of insulin in people with
type two diabetes, there is a high risk factor because of the low insulin
resistance within the brain. This low resistance means the neurons metabolism
is slowed which an adverse effect on the pathways has used to send signals by
means of insulin. (Roskey, n.d.)


It’s only in
the last 20 years that brain injuries have started to cause any concern in contact
sports such as American football, boxing and ice hockey (,
Recent studies have shown that Parkinson’s and dementia develop more frequently
in people who get concussed playing high contact sports such as the ones mentioned
above. “We found that having a concussion was associated with lower
cortical thickness in brain regions that are the first to be affected in
Alzheimer’s disease,” Dr Jasmeet Hayes the assistant professor of
psychiatry at BUSM explained “Our results suggest that when combined with
genetic factors, concussions may be associated with accelerated cortical
thickness and memory decline in Alzheimer’s disease relevant areas.” (Boston
~University Medical Centre, 2017)




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Picture reference
Fig.20) Alzheimer’s medication. Retrieved from: accessed on 17/01/18
Fig.21) Amyloid beta and Alzheimer’s disease.
Retrieved from:
accessed on 21/01/18
Fig.22) Nerve cell. Retrieved from:
accessed on 19/01/18
Fig.23) Neurofibrillary tangle. Retrieved from: accessed on 24/01/18
Fig.24) Oxidative medicine. Retrieved from:
accessed on 27/01/18