1. Alzheimer’s Disease Putting the pieces together
Catherine Nelson, RN

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

3. 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.

4. 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.
Faces of AD

5. Faces and Facts

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

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

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

9. Brain Anatomy & Physiology
Normal Brain Tissue
Neuron Function
Lobe Function
The Hippocampus
Anatomy & Physiology
Used with permission.

10. Used with permission of Dr. Karen Myhr, Wayne State University
Neurons: Messengers of the brain
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

11. 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
Parietal Lobe
Frontal
Lobe
Occipital
Lobe
Temporal
Lobe
Cerebellum
Used with permission

12. 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

13. Used with permission.
text/health/alzheim/brain.gif

14. Check your knowledge Neuron Function
True or False
The neurons collect information and transmit
it through the brain.
TRUE
FALSE

15. Check your knowledge Neuron Function
Right!

16. Check your knowledge Neuron Function
Wrong

17. Check your knowledge Hippocampus Function
True or False
The hippocampus houses memory.
TRUE
FALSE

18. Check your knowledge Hippocampus Function
Right!

19. Check your knowledge Hippocampus Function
Wrong

20. Check your knowledge Lobe Function
True or False
The lobes that are most affected by AD are the
frontal and temporal lobes.
TRUE
FALSE

21. Check your knowledge Lobe Function
Right!

22. Check your knowledge Lobe Function
Wrong

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

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

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

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

27. Brain Shrinkage
As the disease develops, the brain shrinks causing damage
to the cortex and hippocampus,
and enlarging
the ventricles.
Used with permission

28. Check your knowledge Disease Development
True or False
Brain shrinkage causes damage to the cortex, hippocampus and enlarges
the ventricles.
TRUE
FALSE

29. Check your knowledge Disease Development
Right!

30. Check your knowledge Disease Development
Wrong

31. 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.

32. Check your knowledge Plaque
True or False
Plaque lies across cell membranes.
TRUE
FALSE

33. Check your knowledge Plaque
Right!

34. Check your knowledge Plaque
Wrong

35. 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.

36. Check your knowledge Amyloid beta (A4)
True or False
When cleaved A4 seeps outside the cell.
TRUE
FALSE

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

38. Check your knowledge Amyloid beta (A4)
Wrong

39. 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.

40. Check your knowledge Neurofibrillary Tangles
True or False
Neurofibrillary tangles cause neuron death.
TRUE
FALSE

41. Check your knowledge Neurofibrillary Tangles
Right!

42. Check your knowledge Neurofibrillary Tangles
Wrong!

43. 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.
More >

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

45. Check your knowledge Tau and Neurons
True or False
Tau and plaque work together to prevent the development of neurofibrillary tangles.
TRUE
FALSE

46. Check your knowledge Tau and Neurons
Right!

47. Check your knowledge Tau and Neurons
Wrong

48. The New Research
Chromosome 21
Chromosome 19
Lipids
Inflammation

49. Genetics The APP Gene Located on chromosome 21.
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.

50. 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.

51. 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.

52. Check your knowledge Genetics
True or False
Early onset AD is caused by mutation to the APP gene on chromosome 21.
TRUE
FALSE

53. 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.

54. Check your knowledge Lipids
True or False
Lipids bind to Tau and contribute to the development of AD.
TRUE
FALSE

55. Check your knowledge Lipids
Right!

56. Check your knowledge Lipids
Wrong

57. 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.

58. 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.
ApoE does not bind to Tau – allowing Amyloid beta precursor protein to form
the neurofibrillary tangles.

59. ApoE 4 and Women
A mutant form of APOE thought to be responsible for late onset AD especially in women.
A 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 times
the AD risk & results in a smaller hippocampus.
APOE4 genotype is three times as likely to develop deposits of amyloid-beta on cerebral vessel walls
which can lead to ischemia.

60. Check your knowledge Genetics ApoE
True or False
Late onset AD is caused by mutation to the ApoE gene
on chromosome 19.
TRUE
FALSE

61. Check your knowledge Genetics ApoE
Right!

62. Check your knowledge Genetics ApoE
Wrong

63. 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.
Hope!
Halliday G, Robinson SR, Shepherd C, Kril J. 2006

64. Check your knowledge Inflammation
True or False
The inflammatory response and AD have microglia cells in common.
TRUE
FALSE

65. Check your knowledge Inflammation
Right!

66. Check your knowledge Inflammation
Wrong

67. 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

68. 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.

69. Check your knowledge NSAIDs
True or False
NSAIDs reduce inflammatory response, inhibit platelet activation and decreases the formation of beta-amyloid.
TRUE
FALSE

70. Check your knowledge NSAIDs
Right!

71. Check your knowledge NSAIDs
Wrong

72. Alzheimer’s disease (AD)
Overview of
Alzheimer’s disease (AD)
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 tangles are twisted strands of another protein that form inside cells.
Brain atrophy and shrinkage results.
New drugs targeting amyloid protein are being developed.

73. References http://www.ahaf.org/alzdis/about/AD_2003.jpg

74. References http://www.clevelandclinicmeded.com/diseasemanagement/
neurology/alzheimers/alzheimer
Holliday G, Robinson SR, Shepherd C, Kril J. 2006
december2004/pg1.html

75. References http://www.portfolio.mvm.ed.ac.uk/studentwebs/
session3/7/Genetics.htm
text/health/alzheim/brain.gif