Alzheimer

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Alzheimers Disease Putting the pieces together

• Catherine Nelson, RN

http//office.microsoft.com/en_us/default.aspx
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Where are we going?
Click on the topic that interests you!

• Alzheimers Facts What do we know?
• Brain Anatomy Physiology.
• Alzheimers Brain Anatomy Physiology.
• New Research
• Whats the future look like?
• References

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What We Know

• 4.5 million people have Alzheimers 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 onsetbefore 65 years of
  age-often by 30s or 40s.
• It can have a late onsetafter 65 years
• of age.

http//www.alz.org/AboutAD/Statistics.asp
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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
http//www.healthywomen.org/healthreport/december2
004/pg1.html
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Faces and Facts
http//office.microsoft.com/en_us/default.aspx
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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
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Right!

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

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Wrong!

• 10 30 is too low.
• 90 is too high.

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Brain Anatomy Physiology

• Normal Brain Tissue

Neuron Function
Lobe Function
The Hippocampus
Anatomy Physiology
Used with permission. http//lbc.nimh.nih.govimage
s/brain.jpg
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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
throughtheir synapses.
Neurons Messengers of the brain
Used with permission of Dr. Karen Myhr, Wayne
State University
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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 http//lbc.nimh.nih.govimages
/brain.jpg
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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
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Used with permission. www.pueblo.gsa.gov/cic
text/health/alzheim/brain.gif
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Check your knowledge Neuron Function

• True or False
• The neurons collect information and transmit
• it through the brain.

TRUE
FALSE
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Check your knowledge Neuron Function

• Right!

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Check your knowledge Neuron Function

• Wrong

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Check your knowledge Hippocampus Function

• True or False
• The hippocampus houses memory.

TRUE
FALSE
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Check your knowledge Hippocampus Function

• Right!

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Check your knowledge Hippocampus Function

• Wrong

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Check your knowledge Lobe Function

• True or False
• The lobes that are most affected by AD are the
• frontal and temporal lobes.

TRUE
FALSE
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Check your knowledge Lobe Function

• Right!

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Check your knowledge Lobe Function

• Wrong

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Alzheimers A P

• 3 Cardinal Signs
• Brain shrinkage.
• Found on neurons
• Neurolitic Plaques.
• Filled with Amyloid-beta protein.
• Neurofibrillary tangles.

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Check your knowledge Alzheimers A P

• True or False
• Alzheimers Disease is responsible for brain
  shrinkage, neurolitic plaques and neurofibrillary
  tangles.

TRUE
FALSE
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Check your knowledge Alzheimers A P

• Right!

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Check your knowledge Alzheimers A P

• Wrong

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Brain Shrinkage

• As the disease develops, the brain shrinks
  causing damage
• to the cortex and hippocampus,
• and enlarging
• the ventricles.

Used with permission http//www.ahaf.org/alzdis/a
bout/AD_2003.jpg
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Check your knowledge Disease Development

• True or False
• Brain shrinkage causes damage to the cortex,
  hippocampus and enlarges
• the ventricles.

TRUE
FALSE
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Check your knowledge Disease Development

• Right!

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Check your knowledge Disease Development

• Wrong

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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.

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Check your knowledge Plaque

• True or False
• Plaque lies across cell membranes.

TRUE
FALSE
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Check your knowledge Plaque

• Right!

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Check your knowledge Plaque

• Wrong

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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
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Check your knowledge Amyloid beta (A4)

• True or False
• When cleaved A4 seeps outside the cell.

TRUE
FALSE
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Check your knowledge Amyloid beta (A4)

• Right!

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Check your knowledge Amyloid beta (A4)

• Wrong

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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
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Check your knowledge Neurofibrillary Tangles

• True or False
• Neurofibrillary tangles cause neuron death.

TRUE
FALSE
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Check your knowledge Neurofibrillary Tangles

• Right!

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Check your knowledge Neurofibrillary Tangles

• Wrong!

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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 gt
http//www.portfolio.mvm.ed.ac.uk/studentwebs/sess
ion3/7/Genetics.htm
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Tau

• In AD, the sticky Tau proteins get tangled up
  with each other.
• Neurofibrillary tangles (NFT) develop and the
  neuron dies.

Used with permission http//www.ahaf.org/alzdis/ab
out/AD_2003.jpg
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Check your knowledge Tau and Neurons

• True or False
• Tau and plaque work together to prevent the
  development of neurofibrillary tangles.

TRUE
FALSE
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Check your knowledge Tau and Neurons

• Right!

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Check your knowledge Tau and Neurons

• Wrong

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The New Research
Chromosome 21
Chromosome 19
Lipids
Inflammation
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GeneticsThe APP Gene

• Mutations in the APP gene are thought to be
• responsible for Type I, Early On-Set AD.
• Also known as Familial Alzheimers Disease.
• A small but significant portion of Alzheimers
  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
appname
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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/geneappname
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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/geneappname
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Check your knowledge Genetics

• True or False
• Early onset AD is caused by mutation to the APP
  gene on chromosome 21.

TRUE
FALSE
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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.

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Check your knowledge Lipids

• True or False
• Lipids bind to Tau and contribute to the
  development of AD.

TRUE
FALSE
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Check your knowledge Lipids

• Right!

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Check your knowledge Lipids

• Wrong

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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
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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.

http//www.aaalz.com/discussion/faq.php?print1
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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.

http//www.alzheimersdisease.com/hcp/about/pathoph
ysiology/risk-factors.jsp?usertrack.filter_applied
trueNovaId7852773720739677271
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Check your knowledge Genetics ApoE

• True or False
• Late onset AD is caused by mutation to the ApoE
  gene
• on chromosome 19.

TRUE
FALSE
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Check your knowledge Genetics ApoE

• Right!

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Check your knowledge Genetics ApoE

• Wrong

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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
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Check your knowledge Inflammation

• True or False
• The inflammatory response and AD have microglia
  cells in common.

TRUE
FALSE
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Check your knowledge Inflammation

• Right!

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Check your knowledge Inflammation

• Wrong

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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
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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.

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Check your knowledge NSAIDs

• True or False
• NSAIDs reduce inflammatory response, inhibit
  platelet activation and decreases the formation
  of beta-amyloid.

TRUE
FALSE
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Check your knowledge NSAIDs

• Right!

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Check your knowledge NSAIDs

• Wrong

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Overview of Alzheimers disease (AD)

• Alzheimers 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 brains 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.

http//www.alz.org/AboutAD/causes.asp
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References

• http//www.ahaf.org/alzdis/about/AD_2003.jpg
• http//www.ahaf.org/alzdis/about/BrainAlzheimer.ht
  m
• http//alzheimers.about.com/od/research/a/inflamma
  tion.htm
• http//www.alzheimers.org/pr03/02.htm
• http//www.alz.org/AboutAD/causes.asp
• http//www.alz.org/AboutAD/Statistics.asp
• http//www.benbest.com/lifeext/Alzheimer.html

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References
http//www.clevelandclinicmeded.com/diseasemanagem
ent/ neurology/alzheimers/alzheimer http//img.co
xnewsweb.com/C/09/77/33/image_1833779.jpg Holliday
G, Robinson SR, Shepherd C, Kril J.
2006 http//ghr.nlm.nih.gov/geneappname http//g
hr.nlm.nih.gov/geneapoe http//www.healthywomen.o
rg/healthreport/ december2004/pg1.html http//lbc
.nimh.nih.govimages/brain.jpg http//office.micros
oft.com/en-us/default.aspx
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References

• http//www.portfolio.mvm.ed.ac.uk/studentwebs/
• session3/7/Genetics.htm
• www.pueblo.gsa.gov/cic text/health/alzheim/brain.g
  if
• http//w3.uokhhsc.edu/pathology/deptlabs/Alzheimer
  /alzheimer_neuritic.htm