Pathology: How Alzheimer’s disease effects the brainApproximately55,000 people in Ireland are affected by Alzheimer’s, a figure which is growing every day. Because this disease is so prominent in our societyit is important for us, as chemists, to not only be aware of the facts andstatistics, but also what chemical reaction and imbalances make this disease asdevastating and fast acting as it is. In people diagnosed with dementia andAlzheimer’s the cerebral cortex is damaged and shrivels up. This isthe outer layer of the brain and plays a key role in memory, attention,perception, cognition, awareness, thought, language, and consciousness. ThisShrinkage is especially severe in the hippocampus, an area of the cortex thatplays a key role in formation of new memories. Also evident from the picture is a growth in the size of the brain’sventricles.
These are fluid filled spaces within the brain and as they growthey further compress the cortex which further contributes to tissue losswithin the brain. But what causes this to happen? (National institute of aging, n.d.) BetaAmyloid, which are peptides of amino acids, are crucially involved inAlzheimer’s disease. Beta-amyloid is a section of a larger protein whichis called amyloid precursor protein or APP. Not much is actually known what servicethis amyloid precursor proteins actually does but from research scientists knowa great deal about how it appears to function. In its complete form, APPextends from the inside to outside of the brain cell by passing through the membranearound the cell.
When APP is “activated” to do its normal job, it is cut byother proteins called Alpha secretase and Gamma secretase into separate,smaller sections that stay inside and outside cells. There are severaldifferent ways APP can be cut by different enzymes. When cut by two certainenzymes in a certain place, the fragment produced is beta-amyloid. PlaquesTheseplaques form when certain proteins within the cell of the neuron are processeddifferently. Normally, the previously mentioned enzyme alpha-secretase cuts theAPP, which releases a fragment while another enzyme, Gamma secretase, also cutsthe protein in a different place. These fragments are thought to benefitneurons. However, in the cells of an Alzheimer’s patient, the first snip of theprotein is made usually by another enzyme Beta secretase.
(md current, n.d.)Thisenzyme plays a crucial role in the formation of sleeves of fatty tissues calledmyelin sheaths which encase the nerve cells protecting it from viruses anddisease. (Alzheimers universal, 2010) When Beta secretasecleaves the APP, combined with the cut made by gamma secretase, this results inthe release of short fragments called beta amyloid.
(webmd, n.d.) Beta amyloidfragments then come together and become insoluble eventually forming clumps andplaques. (Cognitive disorders, n.d.
) NeurofibrillarytanglesAnotherleading cause of Alzheimer’s are neurofibrillary tangles. These are createdwhen a protein called Tau is modified. In normal brain cells, these proteins arecrucial in the structural integrity of the cells internal transport system.Nutrients and other cellular cargo are carried up and down structures calledmicrotubules to all parts of the neuron. In Alzheimer’s patients, abnormal Tauseparates from the microtubules causing them to fall apart. Strands of thisthen dislodged Tau clump together and becomeinsoluble to form tangles inside the neuron which can block the transport system.(Bailly, n.d.
)The furthest away nerve endings from thenucleus of the cell, which are at the end of the axon, are the firstmicrotubules to disintegrate. As time ges on the destruction travels up theaxon moving closer to the nucleus. (Alzheimers universal, 2010) As a result, communicationbetween the nerve endings and the cell brain is reduced and, once theentire neuron has degenerated, cut off completely. (md current, n.d.)(Alzheimer’s Universal, n.
d.) There areother cells within the brain which are tasked with clearing debris and otherunwanted particles. These cells are called astrocyte and microglia. As themicroglia 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 thenreact to the overwhelmed microglia but the damage is already done. With thesedefence cells disabled, Neurons eventually lose their ability to transportnutrients 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 tissueloss within the brains cerebral cortex, and more precisely, the hippocampus.Othercontributing factorsYears of research has pointed towardsneurofibrillary tangles and beta-amyloid plaques being the two maincontributing factors in the formation of Alzheimer’s disease, however, thereare several other reasons responsible. (Roskey, n.
d.)NeuroinflammationOther thanbeta-amyloid and the tau protein, Neuroinflammation is the third most prominentcontributing factor in Alzheimer’s disease. When the APP’s are cut, they tendto deposit in the A? plaques. The APPprotein previously mentioned, is released within the brain following aconcussion or other trauma.
The effects of neuroinflammation are controlled bymicroglial cells which are a potent generator of free radicals. Studies haverevealed a number of abnormalities in the microglial cells reaction to Alzheimer’sdisease. These abnormalities are triggered by Beta-amyloid and tau and in turnhelp them to spread throughout the brain. (Neuropthology, 2016) FreeRadiclesAs the brain ages,it is put der stress by oxidation which in turn causes small mitochondrial DNAmutations. This process is speeded up in patients with Alzheimer’s disease bythe presence of Beta-amyloid plaques and the previously mentioned microglia (Neuropthology, 2016)DiabetesBecause of low levels of insulin in people withtype two diabetes, there is a high risk factor because of the low insulinresistance within the brain.
This low resistance means the neurons metabolismis slowed which an adverse effect on the pathways has used to send signals bymeans of insulin. (Roskey, n.d.)BraininjuryIt’s only inthe last 20 years that brain injuries have started to cause any concern in contactsports such as American football, boxing and ice hockey (Biography.com, n.d.).Recent studies have shown that Parkinson’s and dementia develop more frequentlyin people who get concussed playing high contact sports such as the ones mentionedabove.
“We found that having a concussion was associated with lowercortical thickness in brain regions that are the first to be affected inAlzheimer’s disease,” Dr Jasmeet Hayes the assistant professor ofpsychiatry at BUSM explained “Our results suggest that when combined withgenetic factors, concussions may be associated with accelerated corticalthickness and memory decline in Alzheimer’s disease relevant areas.” (Boston ~University Medical Centre, 2017) Bibliography Alzheimers universal, 2010. inside the brain.
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