Alzheimers Paper Print

Jonathan Bialick Intro Behavioral Neurosciene PSY M02 Tuesdays and Thursdays 1:00-2:15 Fall 2009

Alzheimer’s Disease

Alzheimer’s disease is a brain disease with symptoms of memory loss, cognitive deterioration, and inability to perform mundane tasks. Over 5.3 million people living in America have Alzheimer’s disease (AD). AD affects people over the age of 60. The likelihood of getting AD doubles every 5 years after a person turns 65. For every 8 people passed the age of 65, one of them has AD. It is believed that people with AD typically die years sooner than those without it. There are two types of AD, early (40s60s) and late onset (70s-80s). While this tragic disease has no cure for now, research is being done at many pharmaceutical companies and universities to find a cure. (Alzheimer’s Basics, 2009, P. 1) AD gets more severe over time, and more symptoms begin to appear. At first, a person with AD begins to have memory problems. This memory trouble spawns from the brain’s diminishing connection to the hippocampus (the center for long-term memory in the brain). When the neurons in the hippocampus loose their link to the rest of the brain, they begin to die off. Once the hippocampus cells die, a person with AD will have trouble remembering minute details, such as what month it is or what they had for dinner last night. (Clinical Application: Acetylcholine and Alzheimer's Disease, 2000, p.1) After the hippocampus is damaged, the disease starts to affect the cerebral cortex. The cerebral cortex helps us speak and think by processing sensory information such as sight and sound. The cerebral cortex also contains the parts of the brain that provide voluntary movement, along with balance and coordination. When the cerebral cortex is affected by AD, a person will loose their ability to speak properly or think rationally. Since the cerebral cortex also provides signals to motor neurons, the ability to stop one’s

self from urinating or contracting a bowel movement is also lost. (Functional Divisions of the Cerebral Cortex, 2008, p. 1) As the damage to the hippocampus and cerebral cortex grows, a person with AD will fail to recognize family members and friends. At this stage, a sufferer will need assistance with eating and taking care of personal hygiene. In AD’s final stages, the disease removes one’s entire ability to communicate. This is not an attitude problem that can be improved upon with therapy, but a physical one that is permanent. (Functional Divisions of the Cerebral Cortex, 2008, p. 1) Alzheimer’s disease occurs when plaques and tangles get caught in the synapses in the brain, cutting off the communication between neurons. Neurons are the senders and receivers of signals, impulses, and messages in the body. A synapse is a gap between two neurons where information travels from one neuron to the other. (Kalat, J, Biological Psychology, 2008, p. 38) Plaques are formed when Amyloid Beta (Aβ) proteins clump together. In the brain, Aβ proteins are normally produced by ribosomes. Amyloid proteins are typically soluble in water, so while everyone has them, they only pose a threat to the brain when they become solid. Phyllis Brown, a reporter for UC News, wrote that Amyloid proteins only clump when there is a problem with the way the proteins are folded. White blood cells and Aceytlcholine (ACh) normally break AB proteins down. The exception in patients with Alzheimer’s is that there is an excess build up of improperly folded Aβ proteins. Scientists believe that if they stimulate white blood cells in the immune system, additional Aβ proteins will be removed, thus restoring balance to the brain. Also, because ACh is said to target Aβ proteins, decreased ACh levels can cause AD. (Alzheimer’s

disease, November 2009, p. 1) (Cecie Starr, Basic Concepts in Biology Moorpark College Edition, 2007, p. 200) The amount of ACh in the brain decreases with age, so scientists needed a way to keep enough ACh in the brain to fight off AB plaques. After ACh has been released into the synapse and filled in the receptors, a bodily enzyme called acetylcholinesterase (AChE) deactivates ACh by breaking it down into acetate and choline. By using a synthetic drug to inhibit AChE, higher levels of ACh can be maintained in the brain. This theory was brought to reality in 1993 when a FDA approved drug called Tetrahydroaminoacridine (marketed as Cognex or Tacrine) was released. Cognex led to better learning and memory performance from patients in the beginning stages of AD, but did not have as great of an effect on patients in later stages. Cognex also had many unwanted side effects, such as dizziness, diarrhea, and vomiting. (Clinical Application: Acetylcholine and Alzheimer's Disease, 2006, p. 1) In 1996 Pfizer’s Donepezil (marketed as Aricept) was released, and currently is the most commonly prescribed medication for AD. Aricept inhibits AChE enzymes by binding to them, which puts the AchE enzymes out of order. Aricept has the same benefits for learning and memory as Cognex, but with fewer side effects. (About ARICEPT, 2008, p.1) Tangles come from chemical changes being made to certain tau proteins that turn them from liquid to solid. A major purpose of tau proteins is to assist microtubules in transporting molecules such as nutrients from one end of a cell to the other. Normally two microtubules run parallel and have tau proteins between them, like rungs of a ladder. If the tau proteins are chemically changed, the microtubule ladder twists and tangles due to

a lack of structural support. Eventually, the microtubule pathway is non-functional, and the surrounding nerve cells do not get the nourishment they need to survive. Researches believe the corruption of tau is caused by genetic mutation. (Alzheimer’s FAQs 2007, p. 1) There are two types of Alzheimer’s: Early and late on-set. Late on-set AD shows up after a person turns 65. According to Alzheimer’s Association spokeswoman Marylin Albert, genetics have an effect on one’s chances of developing AD. Genetics are more likely to cause early on-set AD than they are late on-set AD. If someone inherits the genetic variations linked to AD, he/she can develop early on-set AD while in his or her 40s. (Scientists Identify Two Gene Variants Associated with Alzheimer’s Risk, 2009, p. 1) A person’s genes can affect their chances of having AD. Early on-set AD is autosomal dominant, meaning that it only takes a single mutated gene (Out of four genes total) from two parents for a child to have a 50% chance of getting early on-set AD. Scientists found that a family with AD all had the Amyloid beta (A4) precursor protein (APP) gene mutation. The most widespread APP gene mutation causes the wrong amino acid to be used in an AB protein, which can produce extra large AB proteins that are more prone to clumping. (APP November 2009, p. 1) A mutation in the presenilin 1 (PSEN1) gene is said to be present in around 70 percent of early on-set AD patients. If the PSEN1 gene is not working correctly, the Amyloid precursor proteins do not get developed properly. According to the article PSEN1 (2009) “Defective presenilin 1 disrupts the processing of Amyloid precursor

protein, leading to the overproduction of Amyloid beta peptide.” p. 1 This leads to pieces of defunct AB proteins left to clump together in the brain. (PSEN1, November 2009, p. 1) The Apolipoprotein E (APOE) gene has certain variations that have shown to increase one’s odds of developing AD. Apolipoprotein E’s function is that it fuses with lipids to form very low density lipoproteins (VLDLs), which send lipids like cholesterol from the blood stream to the liver. There are three key APOE gene variations: APOE e2, APOE e3, and APOE e4. There has not been evidence suggesting a connection between APOE e2 and AD, although e2 is implicated in a cholesterol related disease called Hyperlipoproteinemia type III. The e3 gene is said to be the most common APOE gene as the majority of the population has it. Researchers at Columbia University found the APOE e4 allele is most likely to have a detrimental impact on the brain in the beginning stages of AD. The e4 gene is linked to a higher number of Amyloid plaques in the brain. (APOE, 2009, p. 1) (APOE _4 allele predicts faster cognitive decline in mild Alzheimer disease, 2008, p. 1) There are measures to take to lower one’s likelihood of getting late on-set AD. They are similar to the steps one should take to prevent heart attacks. Exercising routinely is recommended, as well as eating a diet with a lot of vegetables. Transfats and saturated fats must be avoided. Maintaining a healthy weight is also important. The Nun Study has shown that people who went to college and read on a regular basis were less likely to develop symptoms of AD. Nuns lacking symptoms of AD had the physical plaques and tangles caused by the Aβ and tau proteins, but did not suffer dementia or any other AD related problem. (Can Alzheimer's Disease be Prevented?, 2009, p. 2)

Alzheimer’s Disease is a serious medical problem for the elderly, and a tough science problem for researchers. Thankfully, AD was discovered over a century ago. The past 100 years of research has given scientists time to hypothesize and test the foundation of knowledge we rely upon today to treat AD. It all started when Dr. Alois Alzheimer and Franz Nissl began studying diseases of the nervous system underneath a microscope in the late 1800s. In 1906, Alois described a disease of the cerebral cortex that he linked to plaques found in brain tissue samples from a 51 year old patient who passed away in the local mental asylum. In the 1990s pharmaceuticals were released to treat AD, but even today the medicines are far from a cure. For the future, scientists predict that gene sequencing will be available to everyone. This means that scientists will be able to use computers to compare the DNA of large groups of people with AD to groups without AD, and spot the differences. By using larger amounts of genetic information, researchers may find more alleles and proteins linked to Alzheimer’s Disease, and in turn have more traction to prevent and eliminate the disease. (The Role of Genetics in Alzheimer's, 2009, p. 1) (Dr. Alois Alzheimer - His Life and Work, 2006, p. 1)

References About ARICEPT (2008), p.1 http://www.aricept.com/about.html Alzheimer’s Disease, (2009, November), p. 1 Retrieved from http://ghr.nlm.nih.gov/ condition=alzheimerdisease APOE (2009, November), p. 1, Retrieved from http://ghr.nlm.nih.gov/gene=apoe APP (2009, November), p. 1 Retrieved from http://ghr.nlm.nih.gov/gene=app Betty Zimmerberg (2007, January 4), Clinical Application: Acetylcholine and Alzheimer's Disease, p. 1 Can Alzheimer's Disease be Prevented? (2009), p. 2, Retrieved from http://www. nia.nih.gov/Alzheimers/Publications/ADPrevented/riskfactors.htm Cecie Starr, Basic Concepts in Biology Moorpark College Edition (2007), p. 200 Clinical Application: Acetylcholine and Alzheimer's Disease (2006), p. 1 Dr. Alois Alzheimer - His Life and Work, (2006), p. 1 Eric H. Chudler (2008), Functional Divisions of the Cerebral Cortex, 2008 F.A.Q. - Nun study, (2008, December 15) p. 1 Kalat, J, Biological Psychology (2008) p. 338 National Institute on Aging (2009), Alzheimer’s-Basics, p. 1 National Institutes of Health (2009), Scientists Identify Two Gene Variants Associated with Alzheimer’s Risk, 2009, p. 1 PSEN1 November (2009), p. 1 Retrieved from http://ghr.nlm.nih.gov/gene=psen1 The Role of Genetics in Alzheimer's (2009), p. 1

UC Davis, Alzheimer’s FAQs (2007), p. 1