Transcript Alzheimer`s Disease

Alzheimer’s Disease
Putting the pieces together
http://office.microsoft.co
m/en_us/default.aspx
Catherine Nelson, RN
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

What We Know
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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
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/december2004/pg1.html
Faces and Facts
http://office.microsoft.com/en_us/default.aspx
Check your knowledge

What percentage of nursing home
placements are due to AD?
Click on the answer

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A.
B.
C.
D.
50%
10%
30%
90%
Right!
 Friends
and family members
can care for people with
different diseases but when
AD is added, care becomes
unmanageable in the home
setting.
Wrong!
10% & 30% is too low.
90% is too high.
Brain
Anatomy & Physiology
Normal Brain Tissue
Neuron Function
Lobe Function
The Hippocampus
Anatomy & Physiology
Used with permission.
http://lbc.nimh.nih.govimages/brain.jpg
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
Lobe Function and AD
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Different areas of the
brain are responsible
for different functions.
AD attacks neurons in
the regions of the
brain that control:

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thought
memory
speech
The areas most
affected:
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frontal lobes
temporal lobes
Parietal
Lobe
Frontal
Lobe
Occipital
Temporal
Lobe
Lobe
Cerebellum
Used with permission
http://lbc.nimh.nih.govima
ges/brain.jpg
Hippocampus
The Computer Center

Responsible for:

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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
Used with permission.
www.pueblo.gsa.gov/cic
text/health/alzheim/brain.gif
Check your knowledge
Neuron Function
 True
or False
 The
neurons collect
information and transmit
it through the brain.
TRUE
FALSE
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Neuron Function
Right!
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Neuron Function
Wrong
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Hippocampus Function
 True
or False
 The
hippocampus houses
memory.
TRUE
FALSE
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Hippocampus Function
Right!
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Hippocampus Function
Wrong
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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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Lobe Function
Right!
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Lobe Function
Wrong
Alzheimer’s A & P
3 Cardinal Signs
 Brain
shrinkage.
 Found on neurons
Neurolitic Plaques.

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Filled with Amyloid-beta protein.
Neurofibrillary tangles.
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
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Alzheimer’s A & P
Right!
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Alzheimer’s A & P
Wrong
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/alz
dis/about/AD_2003.jpg
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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Disease Development
Right!
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Disease Development
Wrong
Plaques
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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.
Check your knowledge
Plaque
 True
or False
 Plaque
lies across cell
membranes.
TRUE
FALSE
Check your knowledge
Plaque
Right!
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Plaque
Wrong
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
Check your knowledge
Amyloid beta (A4)
 True
or False
 When
cleaved A4 seeps
outside the cell.
TRUE
FALSE
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Amyloid beta (A4)
Right!
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Amyloid beta (A4)
Wrong
Neurofibrillary Tangles

Composed of Tau protein and amyloid
deposits.
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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
Check your knowledge
Neurofibrillary Tangles
 True
or False
 Neurofibrillary
neuron death.
TRUE
tangles cause
FALSE
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Neurofibrillary Tangles
Right!
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Neurofibrillary Tangles
Wrong!
Tau and Neurons
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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 >
http://www.portfolio.mvm.ed.ac.uk/studentwebs/session3/7/Genetics.htm
Tau
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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/about/AD_2003.jpg
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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Tau and Neurons
Right!
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Tau and Neurons
Wrong
The New Research
Chromosome 21
Chromosome 19
Lipids
Inflammation
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 onset.
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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
APP Gene Mutation
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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 brainblood barrier to increase the
vasoconstriction in arteries.
http://ghr.nlm.nih.gov/gene=app#name
APP Gene Mutation
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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
Check your knowledge
Genetics
 True
or False
 Early
onset AD is caused by
mutation to the APP gene on
chromosome 21.
TRUE
FALSE
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.

Check your knowledge
Lipids
 True
or False
 Lipids
bind to Tau and
contribute to the development
of AD.
TRUE
FALSE
Check your knowledge
Lipids
Right!
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Lipids
Wrong
Genetics
Apolipoprotein E (ApoE)

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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
Apolipoprotein E
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Theories about how ApoE may work:
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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?print=1
ApoE 4 and Women
o 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.
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/riskfactors.jsp?usertrack.filter_applied=true&NovaId=7852773720739677271
Check your knowledge
Genetics ApoE
 True
or False
 Late
onset AD is caused by
mutation to the ApoE gene
on chromosome 19.
TRUE
FALSE
Check your knowledge
Genetics ApoE
Right!
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Genetics ApoE
Wrong
Inflammation
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
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 antiinflammatory drugs reduce the inflammatory
response of these cells.
Hope!
Halliday G, Robinson SR, Shepherd C, Kril J. 2006
Check your knowledge
Inflammation
 True
or False
 The
inflammatory response
and AD have microglia cells in
common.
TRUE
FALSE
Check your knowledge
Inflammation
Right!
Check your knowledge
Inflammation
Wrong
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.

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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
Non-Steroidal
Anti-Inflammatory Drugs
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Some studies show:
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Researchers caution:
NSAIDS may delay the

onset of AD.
NSAIDS may slow the
progression of the disease.
NSAIDS may reduce the
risk of developing the
disease.
All NSAIDS can cause
stomach irritation,
gastrointestinal
bleeding, heart attack,
and stroke.
Check your knowledge
NSAIDs
 True
or False
 NSAIDs
reduce inflammatory
response, inhibit platelet
activation and decreases the
formation of beta-amyloid.
TRUE
FALSE
Check your knowledge
NSAIDs
Right!
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NSAIDs
Wrong
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.
http://www.alz.org/AboutAD/causes.asp
References
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http://www.ahaf.org/alzdis/about/AD_2003.jpg
http://www.ahaf.org/alzdis/about/BrainAlzheimer.htm
http://alzheimers.about.com/od/research/a/inflammation.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
References
http://www.clevelandclinicmeded.com/diseasemanagement/
neurology/alzheimers/alzheimer
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
References



http://www.portfolio.mvm.ed.ac.uk/studentwebs/
session3/7/Genetics.htm
www.pueblo.gsa.gov/cic text/health/alzheim/brain.gif
http://w3.uokhhsc.edu/pathology/deptlabs/Alzheimer/alz
heimer_neuritic.htm