Alzheimer’s Disease Alzheimer’s Disease Putting the pieces together Catherine Nelson, RN m/en_us/default.aspx

Alzheimer’s DiseaseAlzheimer’s DiseasePutting the pieces together

Catherine Nelson, RNCatherine Nelson, RNhttp://office.microsoft.com/en_us/default.aspx

Where are we going?Where are we going?

Alzheimer’s Facts – What do we know? Brain Anatomy & Physiology. Alzheimer’s Brain Anatomy & Physiolog

y. New Research What’s the future look like? References

Click on the topic that interests you!

What We What We KnowKnow 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 What We Know Know (continued)(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

Faces and FactsFaces and Facts

http://office.microsoft.com/en_us/default.aspx

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

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 Brain Anatomy & PhysiologyAnatomy & Physiology

Normal Brain Tissue

Anatomy & Physiology

Neuron Function

Lobe Function

The Hippocampus

Used with permission.

http://lbc.nimh.nih.govimages/brain.jpg

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.

Used with permission of Dr. Karen Myhr, Wayne State University

Neurons: Neurons: Messengers of the brainMessengers of the brain

Frontal

Lobe

Parietal Lobe

Occipital

LobeTemporal

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.govimages/brain.jpg

HippocampusHippocampus 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 or FalseThe neurons collect

information and transmit it through the brain.

TRUE FALSE


Right!


Wrong

Check your knowledge Hippocampus FunctionTrue or False

The hippocampus houses memory.

TRUE FALSE

Check your knowledge Hippocampus Function

Right!

Check your knowledge Hippocampus Function

Wrong

Check your knowledge Lobe Function

True or FalseThe lobes that are most

affected by AD are the frontal and temporal lobes.

TRUE FALSE


Right!


Wrong

Alzheimer’s A & PAlzheimer’s A & P

3 Cardinal Signs Brain shrinkage. Found on neurons

Neurolitic Plaques.Filled with Amyloid-beta protein.

Neurofibrillary tangles.

Check your knowledge Alzheimer’s A & PTrue or False

Alzheimer’s Disease is responsible for brain shrinkage, neurolitic plaques and neurofibrillary tangles.

TRUE FALSE

Check your knowledge Alzheimer’s A & P

Right!

Check your knowledge Alzheimer’s A & P

Wrong

Used with permission http://www.ahaf.org/alzdis/about/AD_2003.jpg

Brain Shrinkage As the disease

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

Check your knowledge Disease DevelopmentTrue 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

Wrong

PlaquesPlaques 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 PlaqueTrue or False

Plaque lies across cell membranes.

TRUE FALSE

Check your knowledge Plaque

Right!

Check your knowledge Plaque

Wrong

Amyloid beta (A4)Amyloid beta (A4)Amyloid beta precursor protein (APP)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.


Check your knowledge Amyloid beta (A4)

True or FalseWhen cleaved A4 seeps

outside the cell.

TRUE FALSE


Right!


Wrong

Neurofibrillary TanglesNeurofibrillary 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.


Check your knowledge Neurofibrillary Tangles

True or FalseNeurofibrillary tangles cause

neuron death.

TRUE FALSE


Right!


Wrong!

Tau and NeuronsTau 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 >

In AD, the sticky Tau proteins get tangled up with each other.

Neurofibrillary tangles (NFT) develop and the neuron dies.

TauTau

Used with permission http://www.ahaf.org/alzdis/about/AD_2003.jpg

Check your knowledge Tau and NeuronsTrue or False

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

TRUE FALSE

Check your knowledge Tau and Neurons

Right!

Check your knowledge Tau and Neurons

Wrong

The New ResearchThe New Research

Chromosome 21Chromosome 21

Chromosome 19Chromosome 19

LipidsLipids

InflammationInflammation

GeneticsGeneticsThe APP GeneThe 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

APP Gene MutationAPP 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

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 LipidsThe 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 LipidsTrue or False

Lipids bind to Tau and contribute to the development of AD.

TRUE FALSE

Check your knowledge Lipids

Right!

Check your knowledge Lipids

Wrong

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 Amyloid beta precursor protein to form the neurofibrillary tangles.

http://www.aaalz.com/discussion/faq.php?print=1

o A mutant form of APOE thought to be responsible A mutant form of APOE thought to be responsible for for late onset AD especially in women.late onset AD especially in women.

• A woman with one APOE4 allele has 4 A woman with one APOE4 allele has 4 times times

the AD risk of a woman with no allele.the AD risk of a woman with no allele.• A woman with two APOE4 allele has 16 A woman with two APOE4 allele has 16 times times

the AD risk & results in a smaller the AD risk & results in a smaller hippocampus.hippocampus.

o APOE4 genotype is three times as likely to develop APOE4 genotype is three times as likely to develop deposits of amyloid-beta on cerebral vessel walls deposits of amyloid-beta on cerebral vessel walls

which can lead to ischemia.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

Check your knowledge Genetics ApoETrue or False

Late 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

Wrong

InflammationInflammation 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!

True or FalseThe inflammatory response

and AD have microglia cells in common.

Check your knowledge Inflammation

TRUE FALSE

Right!


Wrong


HopeHope for for Alzheimer's DiseaseAlzheimer'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:

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.

Check your knowledge NSAIDsTrue 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

•Alzheimer’s disease begins to damage the brain long before Alzheimer’s disease begins to damage the brain long before symptoms appear. The cells that process information have already symptoms appear. The cells that process information have already begun to deteriorate and die. The hallmarks of AD are two abnormal begun to deteriorate and die. The hallmarks of AD are two abnormal microscopic structures called "plaques" and "tangles" . microscopic structures called "plaques" and "tangles" .

•The amyloid plaques are clumps of protein that accumulate outside The amyloid plaques are clumps of protein that accumulate outside the brain’s nerve cells. the brain’s nerve cells.

•The tangles are twisted strands of another protein that form inside The tangles are twisted strands of another protein that form inside cells. 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.

OverviewOverview of of Alzheimer’s disease (AD)Alzheimer’s disease (AD)

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

ReferencesReferences

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

ReferencesReferences

http://www.clevelandclinicmeded.com/diseasemanagement/neurology/alzheimers/alzheimer

http://img.coxnewsweb.com/C/09/77/33/image_1833779.jpgHolliday G, Robinson SR, Shepherd C, Kril J. 2006http://ghr.nlm.nih.gov/gene=app#namehttp://ghr.nlm.nih.gov/gene+apoehttp://www.healthywomen.org/healthreport/

december2004/pg1.htmlhttp://lbc.nimh.nih.govimages/brain.jpghttp://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/

alzheimer_neuritic.htm

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Alzheimer’s Disease Alzheimer’s Disease Putting the pieces together Catherine Nelson, RN m/en_us/default.aspx