Alzheimers 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!

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

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

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

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

Different areas of the brain are responsible for different functions. AD attacks neurons in the regions of the brain that control:

thought memory speech

Parietal Lobe Frontal Lobe Temporal Lobe Cerebellum Occipital Lobe

The areas most affected:

frontal lobes temporal lobes

Used with permission http://lbc.nimh.nih.govima ges/brain.jpg

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

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

Check your knowledge Neuron Function

True
The

or False

neurons collect information and transmit it through the brain.

TRUE FALSE

Check your knowledge Neuron Function

Right!

Check your knowledge Neuron Function

Wrong

Check your knowledge Hippocampus Function

True
The

or False

hippocampus houses memory.

TRUE

FALSE

Check your knowledge Hippocampus Function

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Check your knowledge Hippocampus Function

Wrong

Check your knowledge Lobe Function

True
The

or False

lobes that are most affected by AD are the frontal and temporal lobes.
TRUE FALSE

Check your knowledge Lobe Function

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Alzheimers A & P
3 Cardinal Signs
Brain

shrinkage. Found on neurons

Neurolitic Plaques.

Filled with Amyloid-beta protein.

Neurofibrillary tangles.

Check your knowledge Alzheimers A & P

True

or False

Alzheimers

Disease is responsible for brain shrinkage, neurolitic plaques and neurofibrillary tangles.
TRUE FALSE

Check your knowledge Alzheimers A & P

Right!

Check your knowledge Alzheimers 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

Check your knowledge Disease Development

Right!

Check your knowledge Disease Development

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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.

Check your knowledge Plaque

True

or False

Plaque

lies across cell membranes.

TRUE

FALSE

Check your knowledge Plaque

Right!

Check your knowledge 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

Check your knowledge Amyloid beta (A4)

Right!

Check your knowledge Amyloid beta (A4)

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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

Check your knowledge Neurofibrillary Tangles

True

or False
tangles cause

Neurofibrillary

neuron death.

TRUE

FALSE

Check your knowledge Neurofibrillary Tangles

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Check your knowledge Neurofibrillary Tangles

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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 >
http://www.portfolio.mvm.ed.ac.uk/studentwebs/session3/7/Genetics.htm

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/about/AD_2003.jpg

Check your knowledge Tau and Neurons

True
Tau

or False

and plaque work together to prevent the development of neurofibrillary tangles.

TRUE FALSE

Check your knowledge Tau and Neurons

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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 Alzheimers Disease. A small but significant portion of Alzheimers Disease which has the characteristic of early onset.

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

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

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

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Check your knowledge Lipids

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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

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?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
Late

or False

onset AD is caused by mutation to the ApoE gene on chromosome 19.

TRUE FALSE

Check your knowledge Genetics ApoE

Right!

Check your knowledge Genetics ApoE

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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 antiinflammatory drugs reduce the inflammatory response of these cells.

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

Check your knowledge Inflammation

True
The

or False

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.

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

Some studies show:

Researchers caution:
All NSAIDS can cause stomach irritation, gastrointestinal bleeding, heart attack, and stroke.

NSAIDS may delay the onset of AD. NSAIDS may slow the progression of the disease. NSAIDS may reduce the risk of developing the disease.

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!

Check your knowledge NSAIDs

Wrong

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

References

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