2. Alzheimer’s Disease Alzheimer’s Disease Putting the pieces together Catherine Nelson, RN http://office.microsoft.co m/en_us/default.aspx

3. Where are we going?  Alzheimer’s Facts – What do we know? Alzheimer’s Facts – What do we know?  Brain Anatomy & Physiology. Brain Anatomy & Physiology.  Alzheimer’s Brain Anatomy & Physiology. Alzheimer’s Brain Anatomy & Physiology.  New Research New Research  What’s the future look like? What’s the future look like?  References References Click on the topic that interests you!

4. What We Know  4.5 million people have Alzheimer’s Disease (AD).  It is responsible for 50% of all nursing home placements.  It can last 20 years.  It can be inherited.  It can have an early onset—before 65 years of age-often by 30’s or 40’s.  It can have a late onset—after 65 years of age. http://www.alz.org/AboutAD/Statistics.asp

5. What We Know (continued)  Late onset AD affects almost half of all people over the age of 85. Given the aging of the baby boomers and the growing number of very old people (80 and above) 11 to 13.1 million Americans will have AD by 2050. http://www.healthywomen.org/healthreport/december2004/pg1.html Faces of AD

6. Faces and Facts http://office.microsoft.com/en_us/default.aspx

7. Check your knowledge  What percentage of nursing home placements are due to AD?  A.50% A.50%  B.10% B.10%  C.30% C.30%  D.90% D.90% Click on the answer

8. Right!  Friends and family members can care for people with different diseases but when AD is added, care becomes unmanageable in the home setting.

9. Wrong! 10% & 30% is too low. 90% is too high.

10. Brain Anatomy & Physiology Normal Brain Tissue Anatomy & Physiology Neuron Function Lobe Function The Hippocampus Used with permission. http://lbc.nimh.nih.govimages/brain.jpg

11. The orange neuron sends information to the yellow neuron at synapses the where neurons touch. The yellow neuron combines the signal from many cells. If the combined signal is large enough, the yellow neuron signals the red neuron through their synapses. Used with permission of Dr. Karen Myhr, Wayne State University Neurons: Messengers of the brain

12. Frontal Lobe Parietal Lobe Occipital Lobe Temporal Lobe Cerebellum Lobe Function and AD  Different areas of the brain are responsible for different functions.  AD attacks neurons in the regions of the brain that control: thought memory speech  The areas most affected: frontal lobes temporal lobes Used with permission http://lbc.nimh.nih.govima ges/brain.jpg

13. Hippocampus Hippocampus The Computer Center  Responsible for: Information processing. Acquiring new memory and retrieval of old memory. Neurofibrillary tangles interfere with and isolate the hippocampus and make it useless. Picture http://www.alzheimers.org/pr03/02./htm

14. Used with permission. www.pueblo.gsa.gov/cic text/health/alzheim/brain.gif

15. Check your knowledge Neuron Function  True or False The neurons collect information and transmit it through the brain. TRUEFALSE

16. Check your knowledge Neuron Function Right!

17. Check your knowledge Neuron Function Wrong

18. Check your knowledge Hippocampus Function  True or False The hippocampus houses memory. TRUEFALSE

19. Check your knowledge Hippocampus Function Right!

20. Check your knowledge Hippocampus Function Wrong

21. Check your knowledge Lobe Function  True or False The lobes that are most affected by AD are the frontal and temporal lobes. TRUEFALSE

22. Check your knowledge Lobe Function Right!

23. Check your knowledge Lobe Function Wrong

24. Alzheimer’s A & P 3 Cardinal Signs  Brain shrinkage. Brain shrinkage  Found on neurons Neurolitic PlaquesNeurolitic Plaques. Filled with Amyloid-beta protein. Filled with Amyloid-beta protein Neurofibrillary tangles. Neurofibrillary tangles

25. Check your knowledge Alzheimer’s A & P  True or False Alzheimer’s Disease is responsible for brain shrinkage, neurolitic plaques and neurofibrillary tangles. TRUEFALSE

26. Check your knowledge Alzheimer’s A & P Right!

27. Check your knowledge Alzheimer’s A & P Wrong

28. Used with permission http://www.ahaf.org/alz dis/about/AD_2003.jpg Brain Shrinkage  As the disease develops, the brain shrinks causing damage to the cortex and hippocampus, and enlarging the ventricles.

29. Check your knowledge Disease Development  True or False Brain shrinkage causes damage to the cortex, hippocampus and enlarges the ventricles. TRUEFALSE

30. Check your knowledge Disease Development Right!

31. Check your knowledge Disease Development Wrong

32. Plaques  Also known as Senile Plaques.  They look like flat clusters of deteriorated nerve terminals which surround an amyloid peptide.  Found in areas of cerebral cortex that are linked to intellectual function.

33. Check your knowledge Plaque  True or False Plaque lies across cell membranes. TRUEFALSE

34. Check your knowledge Plaque Right!

35. Check your knowledge Plaque Wrong

36. Amyloid beta (A4) Amyloid beta precursor protein (APP) Characteristics:  Lie across cell membrane so part is inside the cell and part of it is outside.  Proteins cut APP into pieces and amyloid beta peptides seep outside the cell. http://www.alzheimers.org/pr03/02./htm

37. Check your knowledge Amyloid beta (A4)  True or False When cleaved A4 seeps outside the cell. TRUEFALSE

38. Check your knowledge Amyloid beta (A4) Right!

39. Check your knowledge Amyloid beta (A4) Wrong

40. Neurofibrillary Tangles  Composed of Tau protein and amyloid deposits. Cause senile plaques & accumulate in the cerebral-vascular systems. Resistant to chemical breakdown and absorption. Cause neuron death. http://www.alzheimers.org/pr03/02./htm

41. Check your knowledge Neurofibrillary Tangles  True or False Neurofibrillary tangles cause neuron death. TRUEFALSE

42. Check your knowledge Neurofibrillary Tangles Right!

43. Check your knowledge Neurofibrillary Tangles Wrong!

44. Tau and Neurons  Tau is a protein found in the axon of healthy neurons where it binds to the structure of the neuron “microtubules”. It acts as a crosspiece and stabilizes the neuron structure.  Together, Tau and microtubules act as railway tracks over which information is transported from one part of the neuron to another.  In AD brain cells, microtubules may unravel and develop into neurofibrillary tangles. http://www.portfolio.mvm.ed.ac.uk/studentwebs/session3/7/Genetics.htm More >

45.  In AD, the sticky Tau proteins get tangled up with each other.  Neurofibrillary tangles (NFT) develop and the neuron dies. Tau Used with permission http://www.ahaf.org/alzdis/about/AD_2003.jpg

46. Check your knowledge Tau and Neurons  True or False Tau and plaque work together to prevent the development of neurofibrillary tangles. TRUEFALSE

47. Check your knowledge Tau and Neurons Right!

48. Check your knowledge Tau and Neurons Wrong

49. The New Research Chromosome 21 Chromosome 21 Chromosome 19 Chromosome 19 Lipids Inflammation

50. Genetics The APP Gene  Mutations in the APP gene are thought to be responsible for Type I, Early On-Set AD.  Also known as Familial Alzheimer’s Disease.  A small but significant portion of Alzheimer’s Disease which has the characteristic of early on- set.  Makes the Amyloid Precursor Protein that lies across the cell membrane.  Located on chromosome 21. Used with permission. http://ghr.nlm.nih.gov/gene=app#name

51. APP Gene Mutation  Mutations in the APP gene lead to increased levels of the amyloid beta peptide protein fragments.  These protein products are sticky and tend to “clump”. The clumps are called amyloid plaques and can cross the brain- blood barrier to increase the vasoconstriction in arteries. http://ghr.nlm.nih.gov/gene=app#name

52. APP Gene Mutation  These plaques are found only in Alzheimer disease. The accumulation of amyloid plaques lead to the signs and symptoms of this disease.  Interestingly, these plaques appear to be closely related to structures found in Down's Syndrome. http://ghr.nlm.nih.gov/gene=app#name

53. Check your knowledge Genetics  True or False Early onset AD is caused by mutation to the APP gene on chromosome 21. TRUEFALSE

54. The role of Lipids  Lipids transport cholesterol which is an essential ingredient of all cell membranes. Cholesterol helps membrane fluidity. High levels of cholesterol are associated with increased risk of AD. Cholesterol affects amyloid-beta production by binding to it and contributing to amyloid plaques.

55. Check your knowledge Lipids  True or False Lipids bind to Tau and contribute to the development of AD. TRUEFALSE

56. Check your knowledge Lipids Right!

57. Check your knowledge Lipids Wrong

58. Genetics Apolipoprotein E (ApoE)  APOE is a protein + a fat.  Responsible for metabolism of Very Low Density Cholesterol.  A mutation of APOE – APOE-e4 is thought to be responsible for Type 2 – Late on-Set AD.  Located on chromosome 19. Used with permission. http://ghr.nlm.nih.gov/gene+apoe

59. Apolipoprotein E  Theories about how ApoE may work: ApoE may promote the accumulation of amyloid plaques. ApoE may prevent the removal of amyloid plaques. ApoE may contribute to the development of neurofibrillary tangles. Amyloid beta precursor protein ApoE does not bind to Tau – allowing Amyloid beta precursor protein to form the neurofibrillary tangles. http://www.aaalz.com/discussion/faq.php?print=1

60. oA mutant form of APOE thought to be responsible for late onset AD especially in women. A woman with one APOE4 allele has 4 timesA woman with one APOE4 allele has 4 times the AD risk of a woman with no allele. A woman with two APOE4 allele has 16 timesA woman with two APOE4 allele has 16 times the AD risk & results in a smaller hippocampus. o APOE4 genotype is three times as likely to develop deposits of amyloid-beta on cerebral vessel walls which can lead to ischemia. http://www.alzheimersdisease.com/hcp/about/pathophysiology/risk- factors.jsp?usertrack.filter_applied=true&NovaId=7852773720739677271 ApoE 4 and Women

61. Check your knowledge Genetics ApoE  True or False Late onset AD is caused by mutation to the ApoE gene on chromosome 19. TRUEFALSE

62. Check your knowledge Genetics ApoE Right!

63. Check your knowledge Genetics ApoE Wrong

64. Inflammation  Upon examination, one type of brain cell, the microglia cell, is associated with the plaques in AD.  Researchers are suspicious of this cell because it also participates in classic inflammatory processes.  The good news is that non-steroidal anti- inflammatory drugs reduce the inflammatory response of these cells. Halliday G, Robinson SR, Shepherd C, Kril J. 2006 Hope!

65.  True or False The inflammatory response and AD have microglia cells in common. Check your knowledge Inflammation TRUEFALSE

66. Right! Check your knowledge Inflammation

67. Wrong Check your knowledge Inflammation

68. Hope for Alzheimer's Disease Non-Steroidal Anti-Inflammatory Drugs  Researchers are investigating the use of NSAIDs: Clinical trials are being conducted on Ibuprofen & Naproxen. inhibit platelet activation. decrease the formation of beta - amyloid which compromises the brain-blood barrier and vaso-activity. reduce the inflammatory response of brain cells. Halliday G, Robinson SR, Shepherd C, Kril J.2006

69. Non-Steroidal Anti-Inflammatory Drugs  Some studies show: NSAIDS may delay the onset of AD. NSAIDS may slow the progression of the disease. NSAIDS may reduce the risk of developing the disease.  Researchers caution: All NSAIDS can cause stomach irritation, gastrointestinal bleeding, heart attack, and stroke.

70. Check your knowledge NSAIDs  True or False NSAIDs reduce inflammatory response, inhibit platelet activation and decreases the formation of beta-amyloid. TRUEFALSE

71. Check your knowledge NSAIDs Right!

72. Check your knowledge NSAIDs Wrong

73. Alzheimer’s disease begins to damage the brain long before symptoms appear. The cells that process information have already begun to deteriorate and die. The hallmarks of AD are two abnormal microscopic structures called "plaques" and "tangles".Alzheimer’s disease begins to damage the brain long before symptoms appear. The cells that process information have already begun to deteriorate and die. The hallmarks of AD are two abnormal microscopic structures called "plaques" and "tangles". The amyloid plaques are clumps of protein that accumulate outside the brain’s nerve cells.The amyloid plaques are clumps of protein that accumulate outside the brain’s nerve cells. The tangles are twisted strands of another protein that form inside cells.The tangles are twisted strands of another protein that form inside cells. Brain atrophy and shrinkage results.Brain atrophy and shrinkage results. New drugs targeting amyloid protein are being developed.New drugs targeting amyloid protein are being developed. Overview of Alzheimer’s disease (AD) http://www.alz.org/AboutAD/causes.asp

74. References  http://www.ahaf.org/alzdis/about/AD_2003.jpg http://www.ahaf.org/alzdis/about/AD_2003.jpg  http://www.ahaf.org/alzdis/about/BrainAlzheimer.htm http://www.ahaf.org/alzdis/about/BrainAlzheimer.htm  http://alzheimers.about.com/od/research/a/inflammation.htm http://alzheimers.about.com/od/research/a/inflammation.htm  http://www.alzheimers.org/pr03/02.htm http://www.alzheimers.org/pr03/02.htm  http://www.alz.org/AboutAD/causes.asp http://www.alz.org/AboutAD/causes.asp  http://www.alz.org/AboutAD/Statistics.asp http://www.alz.org/AboutAD/Statistics.asp  http://www.benbest.com/lifeext/Alzheimer.html http://www.benbest.com/lifeext/Alzheimer.html

75. References http://www.clevelandclinicmeded.com/diseasemanagement/ neurology/alzheimers/alzheimer http://img.coxnewsweb.com/C/09/77/33/http://img.coxnewsweb.com/C/09/77/33/image_1833779.jpg Holliday G, Robinson SR, Shepherd C, Kril J. 2006 http://ghr.nlm.nih.gov/gene=app#name http://ghr.nlm.nih.gov/gene+apoe http://www.healthywomen.org/healthreport/ december2004/pg1.html http://lbc.nimh.nih.govimages/brain.jpg http://office.microsoft.com/en-us/default.aspx

76. References  http://www.portfolio.mvm.ed.ac.uk/studentwebs/ session3/7/Genetics.htm  www.pueblo.gsa.gov/cic text/health/alzheim/brain.gif www.pueblo.gsa.gov/cic text/health/alzheim/brain.gif  http://w3.uokhhsc.edu/pathology/deptlabs/Alzheimer/alz heimer_neuritic.htm