"Come alcune notizie possono essere infuriate o irritanti per noi, ma per le persone con malattie neurodegenerative, è una specie di notizia positiva per loro".
"As some news can be infuriate or irritate us but for the people with neuro-degenerative disease , it is kind of a positive news for them."
Diagnosing from the current state, it would be around 135 million worldwide cases of Alzheimer cases in 2050. Life expectancy increase as well as touching the border of 80 causes the prevalence of Alzheimer condition. Before going how this vaccine works, knowing the pathophysiology of Alzheimer can make some sense about the vaccine.
What basically is Alzheimer ?
Alzheimer disease refers to neuro-degenerative condition which means it causes loss of neurons in the cortex part of brain. So, this loss leads to the characteristic symptoms of dementia. Further studies on pathophysiology isn't yet confirmed but some sort of plaques and tangles are oftenly cited for the disease.
Every 4 seconds on earth, someone or the other is diagnosed with the Alzheimer's condition. It has been a major cause of dementia. "Dementia is not a disease ! It's a set of symptoms like difficulty in learning , poor memory condition." Variety of the disease causes some sort of brain cell damage.
In the brain, neuron cells resting on cell membrane gets some "game over" play. In the membrane, we can see a type of protein called as "Amyliod Precursor Protein "(APP) . This protein fits 50% outside the cell membrane and 50% inside of the cell membrane. When some injury occur, APP protein helps in maintaining the neuron by growing and repairing. As Amyloid Precursor Protein is just like other protein, it gets broken down after getting used. This gets broken down and recycles.
Physiological Role of Amyloid beta in Neural cell (credits)
α -secretase when cuts the APP protein and on the other hand γ-secretase cutting the other half of APP protein, it forms a soluble structure which is normal in every individual . The team work by α-secretase and γ -secretase make everything normal as usual which help in repairing actions. But when team work of γ-secretase comes with β-secretase, problem arises. Chopped off particle from β -secretase becomes soluble whereas, portion where γ-secretase enzyme cut remains insoluble. This insoluble particle creates a monomer which is called as Amyloid beta. This monomer becomes so sticky that it goes outside the neurons and bonds with the other monomer. Oligomerization of A β takes place forming plaque called as Beta-Amyloid plaques. [1] / [2]
Histology of Amyloid plaques in Alzheimer (credit)
Beta-Amyloid plaques gets between the neurons in some cases disrupting the neuronal signals. This can lead to condition of impaired brain function. It even evoke immune responses and causes inflammatory condition. Inflammation has some serious role in damaging the surrounding neuronal cells. When these plaques gets deposited around the blood vessels in the brain, it causes amyloid angiopathy. This condition weakens the blood vessel walls and increases the risk of hemorrhage condition and increases blood loos through rupture. Histological figure can be seen of amyloid plaques due to buildup of beta-amyloid which is occurring outside the cell.
Another big part of the Alzheimer disease is tangle. This is found in the cells of neuron.
Tau protein clumps into tangle of tau - Neurofibrillary tangles (crediit)
Neurons are held with one another with a cytoskeleton. This is made up of micro-tubules which provide essential nutrients and molecules along the length of neuronal cell. Here, tau-protein plays a great role in making the pathway. This helps in the other way by creating a channel to make sure the pathway is intact and don't break apart. [3]
When amyloid beta plaque are formed, it activates a pathway inside a neuron cell. It processes onto activation of kinase where an enzyme that transfers phospahate group to the tau protein of micro-tubules. Hyper-phosphorylation of tau protein changes it's shape and completely stops supporting the microtubules. These tau protein clumps together and get tangled with each other showing a characteristic finding of neurofibrillary tangles. Those neurons whose microtubules aren't intact and has tangles in it cannot function as usual and goes to a process of apoptosis. Apopotosis is a process of programmed cell death. [4] / [5]
Summarizing, when the neurons start to go apoptosis in a large scale, the brain change takes place. The cortex shrinks and atropy occurs where the gyri (characteristic ridges of brain) get much narrower. Sulci (grooves between the gyri) also gets wider. When this gets wider, the ventricles which carry cerbro-spinal fluid also gets larger. This all are the characteristic sign that can be seen in the brain of Alzheimer patient.
To the topic :
Sturcture of antibody (credits)
A new vaccine which has the combination of existing anti-tetanus vaccine and a protein from the virus that widely affects variety of plants. The viral protein taken from the plant virus called as "cucumber mosaic virus "(CMV). This has got it's name as it was found in the cucumbers. This has got a worldwide distribution with a vary wide host range. Tetanus epitope is a foreign substance that elicits an immune response. This epitope is incorporated in the CMV particles and tested. The result showed that it cured the psoriasis, allergies.
During the cure of psoriasis and allergies, there were certain IgG anti-bodies that is believed to cure neuro-degenerative disease. A new thought raised in testing this vaccine in the older people. Vaccine increased the levels of IgG which was recognized earlier to fight against this amyloid plaques in the brain of Alzheimer patient.
IgG antibodies are mostly found abundant in the serum which is around 80%-85%. It has various types. I am classifying on the basis of the abundance in serum : IgG1 > IgG2 > IgG3 > IgG4. Whereas according to the disulphide bond : IgG3 > IgG2 > IgG1 = IgG4 . [6]
IgG antibodies reacting with the amyloid beta plaques (credits)
The experiment was done in the Alzheimer patient in controlling the amyloid plaques. The result showed IgG decorating neuritic plaques. Burden to neuritic plaque was decreased which had no increment in the microhaemorrhages rather than increase the phagocytic microglia.
- Result ! Published from : Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
A prophylactic vaccination can be a good approach to public health intervention against the Alzheimer condition. As this condition usually develops from the elderly condition, here it has been optimized only for the older individuals which might be helpful. Further broadening of this preclinical studies to vaccine will be doing on Parkinson's disease which is another neural disease condition. This can also go for various other foreign substances or antigens . [7]
Reference Used:
Mentioned along with the post. For further reference you can visit:
(3) How close are we for the vaccine ?
(4)X-mol : Tetanus epitope incorporating into VLP
(5) Amyloid-β Immunotherapy for the Alzheimer's Disease
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