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IN HIGH SCHOOLS | EDUCATOR GUIDE ALZHEIMER’S acts like prion disease ALZHEIMER’S acts like prion disease EDUCATOR GUIDE About the article The Science News article “Alzheimer’s acts like prion disease,” focuses on the troublesome proteins that accumulate in the brains of people with Alzheimer’s and other neuron-damaging diseases. Recent studies suggest that these proteins behave similar to prions, the infectious culprits behind much rarer, deadly disorders such as Creutzfeldt-Jakob disease, the human form of mad cow disease. Like prions, the proteins that have been linked to Alzheimer’s, Parkinson’s and other ailments are also misfolded, can jump from brain cell to brain cell and, in special circumstances new studies show, might also transfer from person to person. Should they be considered “prion” infections? The recasting could help scientists better understand the disease, but could also generate unwarranted fear. “Alzheimer’s acts like prion Next Generation Science Common Core disease” can be used across From Molecules to Organisms: Structures and Processes: HS-LS1-6 ELA Standards Reading Informational Text for 9–12 Structure and Function: HS-LS1-1, HSLS1-2, HS-LS1-3 ELA Standards Reading for Literacy in Science and Technical Subjects 9–12 a wide range of curricula, including biology, life sciences, and language arts, ELA Standards in Writing for 9–12 (includes using and creating graphs and charts) and can be used to support the following education standards: Prior to reading Guide student reading by first outlining a theme. Point out connections between this article and what students are learning in class. Here, find ideas for a few standard-aligned paths to follow while reading: ss “Alzheimer’s acts like prion disease” explores proteins as infectious agents, but proteins are also essential to all living organisms. Ask students to share what they remember about the role of proteins in the body. How do proteins form from amino acids? (Students should mention the primary, secondary, tertiary and quaternary structures of the protein. They should recall that the chain of amino acids twists and bends and folds at each of these stages to become the protein.) If amino acids and proteins have not yet been addressed in class, the Protein Data Bank offers a good introduction. ss The ability to infect other proteins is a hallmark of prions, but scientists don’t know exactly how one protein makes another misfold. Ask students to think of examples of known infectious agents (viruses, bacteria, parasitic roundworms, ticks, fungi). How do infections spread (through direct physical contact, inhaling infectious particles, in saliva) and what determines how quickly they spread (density of the population, nature of the agent itself, safety measures such as quarantines and immune status are some examples)? ss The words we use to describe something influence how we think about it. Ask the students to consider the importance of a name, particularly as it relates to communicating science. What names stir up negative emotions (ragweed, mad cow disease), and are there others that sound positive or uplifting (the drug Cymbalta, for example)? How do the words that scientists choose to use—whether simple or complex, positive or negative, descriptive or cryptic—affect public understanding of science? After reading: Comprehend You can adapt and print this 1. What is the main topic of the article? (New studies show that the distorted proteins linked to some brain diseases appear to behave like infectious agents, spreading among brain cells and corrupting other proteins. Some scientists think such diseases should be classified among disorders caused by the infectious particles known as prions.) 2. What is a prion? (Proteinaceous infectious particle, a protein with a misfolded form that can cause disease and is infectious) 3. Name one disease known to be caused by prions? (Creutzfeldt-Jakob disease, mad cow, kuru) 4. A buildup of which protein in the brain is linked to Alzheimer’s disease? (A-beta, amyloid-beta) assessment (see Blackline Master #1) to check for comprehension before or after discussion. 5. What does the deformed prion cause normal prions to do? (Change shape into misfolded forms) 6. What is one of the “biggest outstanding mysteries” in this field? (Defining what constitutes an infectious “seed”) After reading: Analyze 1. In the article you learn that prion proteins exist in a normal form in the body. When do they become dangerous and cause disease? (When they “shape-shift” or misfold into dangerous configurations, when they cause other prions to misfold) 2. What are the advantages and disadvantages of classifying neurodegenerative disorders such as Alzheimer’s as prion infections? (Advantages: Recasting Alzheimer’s and other neurodegenerative disorders as prion diseases may help researchers better understand the diseases and may reveal ways to halt or prevent neural destruction. Disadvantages: Prion is a loaded word that comes with a lot of fear. If people think Alzheimer’s and other neurodegenerative diseases are infectious, they might be more afraid of interacting with people with these diseases, sharing hospitals and surgical equipment, or having a research lab nearby.) 3. Should people worry about A-beta and other neurodegenerative-related proteins spreading from person to person in their everyday lives? Why or why not? (In general, no. There is no evidence that this happens in general and only limited evidence that it happens in very special circumstances. Other explanations for the situation documented in the article cannot be ruled out. That being said, more research is needed.) 4. How could hardy (tough) prions pose a problem for hospitals? (According to recent studies, if the disease-causing prions remain on surgical equipment, there appears to be a possibility of them spreading to another patient. This could mean elaborate and costly procedures for decontaminating surgical equipment.) Discuss and Assess After students read the article independently, return as a group to the concepts outlined prior to reading. Invite students to share their answers and observations from the article and lead a class discussion that further underscores your current curriculum. The discussion can serve as an informal assessment. Ideas for further reading discussion or writing prompts include: ss Remind students that prions (proteinaceous infectious particles) are proteins that can have both a normal and misfolded form. Although all proteins are formed by twisting and folding, a “prion” can cause a disease when others do not. The diagram of protein corruption, provided in Blackline Master #2, may be helpful in your discussion. What does the dual nature of proteins mean for our understanding of biology? How do we think about friends versus foes in the body? What other biological agents are helpful or harmful depending on their type or form? (Possible agents include genes that are normal or variant, microbes found in different places in the body and in different abundances, immune reactions that are essential for keeping the body healthy but are also overactive in some diseases.) ss Read the following excerpt from the article and ask students to explain what the author means by “propagate through the brain like prions.” “The results raise the possibility that given the right opportunity, A-beta and other proteins involved in brain disorders, such as the Alzheimer’s-related tau and Parkinson’s-linked alpha-synuclein, may propagate through the brain like prions. Thinking of the proteins involved in neurodegenerative diseases as prions ‘brings conceptual unity to the whole field,’ says neurobiologist Michel Goedert of the University of Cambridge.” How might scientists use this conceptual unity to better understand neurodegenerative diseases? (Answers will vary. For example, scientists might look for similarities in the shape of prions and other disease-linked proteins. Having parallel systems to study might point scientists to the triggers responsible for misfolding. Likewise, researchers might probe the importance of protein accumulation in prion diseases.) ss Consider how a person is treated differently both by science and society when they have an infectious disease. (You might point to the mistreatment of people with leprosy, and policies that kept HIV positive people from traveling to the United States. Also consider discussing the worldwide response to the Ebola epidemic.) Ask the students how they react differently when they are around someone with an infectious disease? Would students treat Alzheimer’s patients differently if they thought there was an infectious component? Extend Offer students other ways to explore the content of the article as it relates to your curriculum, such as: ss Build: As you explore amino acids and proteins through your curriculum, you can add a hands-on component by building your own protein jewelry or sculptures. A basic level version of this activity is to identify several proteins and their amino acids. Assign and provide different colored beads for each amino acid. Students can choose the protein they’d like to build and assemble the beads (on a string for jewelry or a wire for sculptures) according to the proper sequence. For more on how to differentiate an activity like this for your curriculum and for students at various levels, see the “DNA Bracelets” activity from the University of Maryland (here), “Wear A Chimp on Your Wrist” from the University of Leicester (here), and a protein bracelets activity from the Arizona Science Center (here). ss DNA: While amino acids are the building blocks of proteins, ultimately it is DNA that provides the blueprint or “instructional code” to build each protein. Encourage students to build their own paper model DNA. An excellent resource to help facilitate this activity can be found at the Protein Data Bank. Click here. ss Essential: Remind students that our bodies do not make all of the 20 amino acids we need to function properly. We get the amino acids our bodies don’t make, called essential amino acids, from foods. Direct students to research which amino acids we must get from food—and which foods provide the essential amino acids. Students can use the provided chart to record their findings (see Blackline Master #3). A good resource for background information on the chemistry of amino acids can be found from the University of Arizona’s Biology Project (here). ALZHEIMER’S IN HIGH SCHOOLS acts like prion disease Comprehend After reading the article, 1. What is the main topic of the article? 2. What is a prion? 3. Name one disease known to be caused by prions? 4. A buildup of which protein in the brain is linked to Alzheimer’s disease? 5. What does the deformed prion cause normal prions to do? “Alzheimer’s acts like prion disease,” answer these questions: BLACKLINE MASTER #1, P. 1 6. What is one of the “biggest outstanding mysteries” in this field? 1. In the article you learn that prion proteins exist in a normal form in the body. When do they become dangerous and cause disease? 2. What are the advantages and disadvantages of classifying neurodegenerative disorders such as Alzheimer’s as prion diseases? 3. Should people worry about A-beta and other neurodegenerative-related proteins spreading from person to person in their everyday lives? 4. How could hardy (tough) prions pose a problem for hospitals? Analyze Use what you already know about the topic, as well as what you learned in the article “Alzheimer’s acts like prion disease,” and answer these questions: BLACKLINE MASTER #1, P. 2 ALZHEIMER’S IN HIGH SCHOOLS acts like prion disease Protein Corruption Prions (dark blue) can form spontaneously or be introduced into the brain. Prions incite normal versions of the same proteins (light blue) to misfold. These prions aggregate to form clumps of fibrils. This process may be at the heart of neurodegenerative diseases, some researchers propose. SOURCE: M. GOEDERT/SCIENCE 2015, L.C. WALKER AND M. JUCKER/ANNU. REV. NEUROSCI. 2015 Normal protein BLACKLINE MASTER #2 Misfolded Misfolded protein protein seed recruits/morphs normal protein Misfolded proteins accumulate Form fibrils Buildup of fibrils ALZHEIMER’S IN HIGH SCHOOLS acts like prion disease Essential Foods Take 10 minutes to use your textbook and online sources to identify as many essential amino acids as you can find. What foods provide these amino acids? Essential Amino Acid BLACKLINE MASTER #3 Foods that contain Essential Amino Acid