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--- group_5_presentation_2_-_alzheimers [2018/11/01 23:24]
osujic [History]
+++ group_5_presentation_2_-_alzheimers [2018/11/04 18:27] (current)
chuj19 [Alzheimer's Disease]
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 ======= Alzheimer's Disease =======
+{{ :alzheimer-disease.jpg?direct&600 |}}
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 ====== Pathophysiology ======
+**Beta-Amyloid Plaque:**
+Amyloid plaques are extracellular deposits of Beta- amyloid in the brain. In an healthy individual, the transmembrane Amyloid Precursor Protein (APP) undergoes an alpha cleavage leading to sAPPa (soluble Amyloid Precursor Protein alpha) to be sent to the extracellular region and a gamma cleavage releasing AICD (APP Intracellular Domain) into the cell. While the in-between portion becomes P3 - with no known biological functions (Jouanne & Voisin-Chiret, 2017). However, in patients with late-onset Alzheimer's dieases why undergo beta cleavage that cleaves to form sAPPb (soluble APP beta) and gamma cleavage to form AICD (BioLegend, 2018). However this time the  in-between portion becomes 42 Beta-amyloid and accumulate to form the plaque that will cause disturb long-term potentiation, which over time leads to dysfunctional synapse and neuron deaths (Oddo et al., 2003).
+{{ :amyloid_process.jpg?600 |}}
+Figure 1: The APP process in healthy individual (left) verses in late-onset Alzheimer's patient (right)
+**Tau Protein and Neurofibrillary Tangle:**
+Another hallmark of Alzheimer's disease is characterized by the abnormality in the Tau protein. In healthy person the Tau protein act as a regulator for of tubulin which controls the stabilization of microtubules (Wang et al., 2013).  This allows for many cellular dynamic activities such structuring, transporting materials and DNA replication. However, Tau protein is hyperphosphorylated by the overexpression of Tau kinase in Alzheimer's patients (Jouanne & Voisin-Chiret, 2017). This causes these proteins to misfold and aggregate to form neurofibrillary tangles that leads to the loss of neurons in the patient's brain, however the specific mechanism behind this is still unknown.
+{{ :tau.jpg?500 |}}
+Figure 2: The pathway which Tau protein is hyperphosphorylated leading to neurofibrillary tangles. The red lighting represent possible therapeutic targets in treating Alzheimer's disease.
+**APO-E, Genetic Promotor:**
+Another pathogenic gene mutation is also identified to be responsible for in Alzheimer's patients. APO-E or apolipoprotein-e in its wildtype (E3) act as a ligand that regulates the cholesterol level in the cell (Czyzewski et al., 2003). However, this gene is mutated to the E4 form in Alzheimer's patient that ultimately bind with the beta-amyloid to accelerate their aggregation and promote the formation of plaque (Wisniewski et al., 1994). This is important as it describes the genetic connection of the inheritability of the disease and people who may be at higher risk of this neuro-degenerative disease.
+{{ :apoe.jpg?500 |}}
+Figure 3: 3D structure of APO-E4 verus APO-E3
 ====== Drugs and Medication ======
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 {{ :alzheimers-dementia-treatments-synapse-neurons-inlineimage-02.jpg?500 |{{ ::alzheimers-dementia-treatments-synapse-neurons-inlineimage-02.jpg?200 |}}
+Figure 4: Image that represent the relation between synapse, neurons and neurotransmitters.
 **Cholinesterase inhibitors:**
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 The Alzheimer’s Research and Prevention Foundation has established 4 pillars to prevent Alzheimer’s. This foundation is known for researching medical approaches, educating others, and facilitating communication with health care professionals for 20 years. These 4 pillars fall into the category of diet and supplements, physical and mental exercise, yoga and meditation, as well as psychological well-being (Alzheimer’s Research & Prevention Foundation, 2018).
-{{ :logo-arpf-home.jpg?direct&500 |}}        Figure _: The Alzheimer's Research and Prevention Foundation
+{{ :logo-arpf-home.jpg?direct&500 |}}        Figure 5: The Alzheimer's Research and Prevention Foundation
 ==== Pillar 1: Diet and Supplements ====
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 ==== Aducanumab Targeting Beta-amyloid Protein ====
-According to the alzheimer’s association, there are currently many targets and studies being conducted to prevent AD. Beta-amyloid is present in those who have Alzheimer’s by the two enzymes beta-secretase and gamma-secretase which ultimately forms the beta-amyloid protein (Alzheimer’s Association, 2018). Aducanumab, also known as BIIB037, tries to target the aggregated forms of beta-amyloid that can eventually develop into the amyloid plaque. This antibody was derived by a biotech company in Switzerland and has passed its phase 1, 2, and is currently in phase 3 (Alzforum, 2018). A one-year data for the 6 mg/kg dose of aducanumab showed significant reduction in brain amyloid levels  and therefore a study consisting of the phase 3 trials objective is to evaluate how effective doses of aducanumab is in individuals with AD (Alzforum, 2018). This is currently conducted within around 1605 participants with a dosages of monthly intravenous infusions. Furthermore, this drug is still in the research and is not released to the public. This study has started in September 30, 2015, and is expected to be completed by April 30, 2022 (National Library of Medicine, 2018).
+According to the Alzheimer’s Association, there are currently many targets and studies being conducted to prevent AD. Beta-amyloid is present in those who have Alzheimer’s by the two enzymes beta-secretase and gamma-secretase which ultimately forms the beta-amyloid protein (Alzheimer’s Association, 2018). Aducanumab, also known as BIIB037, tries to target the aggregated forms of beta-amyloid that can eventually develop into the amyloid plaque. This antibody was derived by a biotech company in Switzerland and has passed its phase 1, 2, and is currently in phase 3 (Alzforum, 2018). A one-year data for the 6 mg/kg dose of aducanumab showed significant reduction in brain amyloid levels  and therefore a study consisting of the phase 3 trials objective is to evaluate how effective doses of aducanumab is in individuals with AD (Alzforum, 2018). This is currently conducted within around 1605 participants with a dosages of monthly intravenous infusions. Furthermore, this drug is still in the research and is not released to the public. This study has started in September 30, 2015, and is expected to be completed by April 30, 2022 (National Library of Medicine, 2018).
 ==== AADvac1 Targeting Tau Protein ====
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 The function of Tau protein helps to maintain the structure of the neuron. However, within individuals that have AD, the tau protein is abnormal and therefore collapses which destabilizes the structure of neruons (Alzheimer’s Association, 2018). A current drug in research is AADvac1, which is a vaccine that promotes the body’s immune system to help attack these abnormal forms of tau protein. This vaccine has synthetic peptide which is derived from the amino acids 294 to 305 (Alzforum, 2018). This vaccine is currently in the phase 2 safety trial by Axon Neuroscience  where they are currently evaluating the safety and efficacy of AADvac1 with patients who have mild AD (National Library of Medicine, 2018).
-{{ :375px-pdb_1i8h_ebi.jpg?direct&300 |}} Figure _: Picture of the tau protein structure.
+{{ :375px-pdb_1i8h_ebi.jpg?direct&300 |}} Figure 6: Picture of the tau protein structure.
 ====== Conclusion ======
+Although there currently is not a definite cure for Alzheimer's disease, current research such as Aducanumab and AADvac1 shows promising progression with research. Furthermore, other research focusing on the inflammation of the brain with the disease is also being researched and will hopefully pass the trials so patients are able to use the drug. There are also many preventive ways described within the 4 pillars of Alzheimer's Prevention and the management of the patient is just as important.
+====== References ======
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 Alzheimer's Disease. (n.d.). Retrieved from https://www.saintlukeskc.org/condition/alzheimers-disease
+Alzheimer's Disease: Symptoms and Care | Emed Multi Specialty Group. (2018, May 07). Retrieved from https://emedmultispecialtygroup.com/2018/03/20/alzheimers-disease-symptoms-care/
 Alzheimer's Prevention. (2018). Alzheimer's Prevention through Diet and Supplements, Stress Management, Exercise, and Spiritual Fitness. [online] Available at: http://alzheimersprevention.org/4-pillars-of-prevention/ [Accessed 30 Oct. 2018].
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 Imtiaz, B., Tolppanen, A. M., Kivipelto, M., & Soininen, H. (2014). Future directions in Alzheimer's disease from risk factors to prevention. Biochemical pharmacology, 88(4), 661-670.
-JIang, H (2017). Life Sci 3AA3 Essay - Apolipoprotein E (APO-E) isoforms and Alzheimer’s disease (unpublished).
+Jiang, H (2017). Life Sci 3AA3 Essay - Apolipoprotein E (APO-E) isoforms and Alzheimer’s disease (unpublished).
 Jouanne, M., Rault, S., & Voisin-Chiret, A. S. (2017). Tau protein aggregation in Alzheimer's disease: An attractive target for the development of novel therapeutic agents. European journal of medicinal chemistry, 139, 153-167.
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 Li, X. L., Hu, N., Tan, M. S., Yu, J. T., & Tan, L. (2014). Behavioral and psychological symptoms in Alzheimer’s disease. BioMed research international, 2014.
+Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., ... & LaFerla, F. M. (2003). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron, 39(3), 409-421.
 Optometry, F. (2018). Physical Exercise Is Good For Your Eyes – Fresno CA | Fig Garden Optometry. [online] Figgardenoptometry.com. Available at: https://figgardenoptometry.com/2017/03/01/physical-exercise-is-good-for-your-eyes/ [Accessed 30 Oct. 2018].
@@ Line 180: / Line 209: @@
 Reitz, C., Brayne, C., & Mayeux, R. (2011). Epidemiology of Alzheimer disease. Nature Reviews Neurology, 7(3), 137.
+Wang, J. Z., Xia, Y. Y., Grundke-Iqbal, I., & Iqbal, K. (2013). Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. Journal of Alzheimer's Disease, 33(s1), S123-S139.
+Wisniewski, T., Castano, E. M., Golabek, A., Vogel, T., & Frangione, B. (1994). Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. The American journal of pathology, 145(5), 1030.

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