Ever since I was young, there have always been instances of neurodegenerative disease in my family. My great-uncle has suffered from Parkinson’s disease for many years and though Parkinson’s is very debilitating, he has lived with it for a quite a while and embraces it as a part of his identity. He continues to live his life with his family and recently born grandchildren. This, however, is not my motivation to research Alzheimer’s disease. My motivation comes from my paternal grandmother who had a sudden bout of the disease and shortly passed away after showing symptoms of memory loss. I was quite close with my grandmother despite being separated by some 8,700 miles, we talked over the phone nearly every day as casually as if we were friends and we played board games and chatted when we were together in person. As her memory began to fade, it became unmistakably clear just how much Alzheimer’s disease can affect an entire family. Both the maternal and paternal sides of my family watched as we were forgotten and eventually left behind as she departed this world. I was left longing for the grandmother that I considered my best friend, or at least an explanation of what happened to my grandmother from the time she began to lose her memories to the end besides the doctor’s simple explanation: “Alzheimer’s.” Coming up on the third anniversary of her death, I thought this opportunity would be the perfect chance for me to find an explanation to exactly what happens to the brain in Alzheimer’s disease and share that with you.
Alzheimer’s disease is a neurodegenerative disease that generally starts its course of neural destruction in the temporal lobe, more specifically, areas of the brain that are responsible for memory, so the hippocampus is very much affected by Alzheimer’s. As time progresses, more areas of the brain are affected until the patient passes away. Alzheimer’s is characterized by the death of neurons in the brain. The cause for this neuronal death is not yet known, but there are three major associations that modern science has put with Alzheimer’s disease. The first is the presence of something called ß-Amyloid plaques. ß-Amyloid plaques are clumps of an insoluble protein called ß-Amyloid. ß-Amyloid plaques form in between neurons and their synapses. This blocks communication between neurons in the brain, reducing brain function and showing us symptoms such as loss of memory, loss of understanding when viewing images, trouble with speech and writing, along with many other reduced mental capacities. The ß-Amyloid plaques affect the neurons in the brain in another way as well. They activate the immune cells in the brain which try and remove the plaque, but in doing so, they cause inflammation (similar to how when you skin your knee, you may feel some swelling) in the brain which kills nearby neurons. The symptoms caused by this are similar to those aforementioned.
The second association that scientists have made is the relationship between Alzheimer’s and neurofibrillary tangles. Neurofibrillary tangles are formed when the cytoskeleton of a cell is compromised. The cytoskeleton of a cell is analogous to our own skeletons, it supports a cell and gives it a shape that helps it carry out its function. In the cytoskeleton, there are fibers called microtubules attached to a protein called tau, this complex helps to act like the “bones” in the cell. The microtubule and tau complexes help transport food and waste within the cell as well. In Alzheimer’s disease, the microtubules and tau complexes of neurons separate and the fibers of the tau proteins tangle with other nearby tau proteins. This collapses the cell and destroys the intracellular transport system of materials which results in cell death.
The final association scientists have made is between exosomes and ß-Amyloid plaques. It has been seen that cells sometimes take in some of the ß-Amyloid plaque from their surroundings and send it out in exosomes, or bubbles that leave the cell, that carry ß-Amyloid plaque to other places in the brain which spreads the reach and effects of Alzheimer’s disease.
In the two figures up above, we can see the effects of the three Alzheimer’s disease related mechanisms that were mentioned before. In figure 1, we have an MRI scan of healthy brained people (HC) and Alzheimer’s disease patients (AD). Upon a closer look, we can see that the HC subjects have a lot more of the white mass than the black spaces when compared to the AD patients. This means that their brains are simply larger because the neurons in their brains aren’t being destroyed by the disease. In the second figure (PET scan), we can see brain activity by seeing just how much glucose is being used by the neurons in the brain. Bright colors such as red, yellow and green indicate that lots of glucose is being used, this means that neurons are metabolizing glucose to get energy to perform their functions in the brain. This is far more prevalent in the normal brain than the Alzheimer’s brain as there are more neurons alive and in need of energy.
The PET scan and the MRI show evidence that there is neuronal death in the brain, which is ultimately what causes the downhill spiral of brain function in Alzheimer patients.
Alzheimer’s Association [Internet]. 2021. 225 N. Michigan Ave. Floor 17 Chicago, IL 60601: Alzheimer’s Association; [updated 2021; cited 2021 Apr 28]. Available from: https://www.alz.org/national/documents/topicsheet_betaamyloid.pdf
Alzheimer’s Association [Internet]. 2021. 225 N. Michigan Ave. Floor 17 Chicago, IL 60601: Alzheimer’s Association; [updated 2017 Mar; cited 2021 Apr 28]. Available from: https://www.alz.org/alzheimers-dementia/10_signs
Ledig C, Schuh A, Guerrero R, Heckemann R, Rueckert D. 2018. Structural brain imaging in Alzheimer’s disease and mild cognitive impairment: biomarker analysis and shared morphometry database. Nature [Internet]; [cited 2021 Apr 28]. Available from:https://www.nature.com/articles/s41598-018-29295-9
Malm T, Loppi S, Kanninen K. 2016. Exosomes in Alzheimer’s disease. ScienceDirect [Internet]; [cited 2021 Apr 28]. Available from: https://www.sciencedirect.com/science/article/pii/S0197018616300614
Mattson M. 2004. Pathways towards and away from Alzheimer’s disease. Nature [Internet]; [cited 2021 Apr 28]. Available from: https://www.nature.com/articles/nature02621#Sec1
U.S. Department of Health & Human Services [Internet]. 2017. 200 independence Avenue, S.W. Washington, D.C. 20201: U.S. Department of Health & Human Services; [updated 2017 May 16; cited 2021 Apr 28]. Available from: https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease Vickers J, Dickson T, Adlard P, Saunders H, King C, McCormack G. 1999. The cause of neuronal degeneration in Alzheimer’s disease. ScienceDirect [Internet]; [cited 2021 Apr 26]. Available from: https://www.sciencedirect.com/science/article/pii/S0301008299000234
By: Aakash Parthasarathy