Causes of Alzheimer’s Disease

The causes of Alzheimer’s disease are still in question, and the changes that take place in the brain are constantly being studied.  There are several theories about the causes underlying Alzheimer’s disease including:

1. The brain doesn’t make enough acetylcholine, a neurotransmitter.

2. Beta amyloid, shortened forms of a protein, join together to form plaques in the brain.

3. Myelin, an insulating material that surrounds neurons, breaks down.

4. Tau tangles form in the brain.

Let’s discuss that last theory, the tau theory, in more depth.  The tau protein interacts with and stabilizes microtubules, the scaffolding structure of cells.  It is found mostly in neurons.  Two different changes in the tau protein can affect its ability to function normally – isoforms and phosphorylation.

Different isoforms of the tau protein can be present in cells.  Isoforms of tau are different versions of the protein.  They are made when the gene from which the protein is created is cut in various places creating different sequences.  These isoforms have variable structures with different attributes.  Some of the isoforms of tau are more likely to form tangles than others.

The tau protein can also be changed after the protein is made through a process called phosphorylation.  Phosphorylation adds a phosphate group to the tau protein.  If several phosphate groups are added to the protein, tau can self-assemble into the tangles that are characteristic of Alzheimer’s patients.

Tau protein aggregates into filaments (left).  The filaments form tau tangles (right).

Tau tangles can lead to disintegration of microtubules in neurons.  This can then result in malfunctions in the communication between neurons leading to cell death and cognitive impairment seen in Alzheimer’s patients.

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Memories of Grandma

I had another post planned for this week, a post about Alzheimer’s research and new advances in the field.  But on April 1st, I got a phone call.  My grandmother, who has been living with Alzheimer’s for several years, was getting moved to hospice and was not doing well.

The past nine days have been spent visiting her at hospice, hoping for peace and comfort to find her, spending time with aunts, uncles, and cousins, and remembering the grandma we all once knew.

The grandma we remember was the woman who would organize a gigantic garage sale every Memorial Day at their cottage home on the lake.  The woman who would cook in the tiny kitchen at the cottage and feed anyone and everyone who walked through the door.  The woman who would make the world’s best crepes and the most fantastic caramel brownies.  The woman who raised eight kids, took care of her husband, and entertained grandchild after grandchild and never seemed to grow tired.  The woman who always had a kind word and a hug at the ready.

I won’t let Alzheimer’s take my memories, and I will remember the strong, incredible, beautiful woman my grandmother will always be to me.  Even if she has forgotten.

Wisconsin History on the Ice Age Trail

With spring approaching (hopefully), everyone is looking forward to getting outside and taking advantage of all that Wisconsin has to offer in warmer weather.  On the Ice Age Trail, hikers can learn about Wisconsin history while taking a walk through beautiful scenery.

The Ice Age Trail is a hiking corridor that winds through 30 of the 72 counties in Wisconsin including Dane County.

Map of entire Ice Age Trail route when completed

The trail loosely follows the terminal moraine, or furthest advance, of the ice sheet present during the last continental glaciation – the Wisconsin Glaciation.  (For maps of the glaciation, see www.geology.wisc.edu/~davem/abstracts/06-1.pdf.)

It’s called the Wisconsin Glaciation because Wisconsin has some of the most interesting landforms that have survived since the time of the glacial epoch.  Much of the landscape was shaped by the glaciation that ended around 10,000 years ago.

As the ice moved south out of Canada, it split into various lobes.  The lobes stretched in various directions including one over Lake Michigan, one through the Wisconsin Valley and one over Lake Superior.  Many features of the Wisconsin landscape are a result of the impact of these lobes of ice on the earth.

The landscapes interpreted by the trail include forested areas, agricultural lands, prairies and wetlands.  On a segment of the trail near Devil’s Lake, a 25,000-year-old landscape can be found within a mile of a landscape that dates back 2 billion years.  These features allow hikers to witness landforms of various historical ages.

56 people have hiked the entire length of the trail (around 1,200 miles), but only about 640 miles are authorized as official segments of the Ice Age Trail.  New sections of trail are created around interesting features thus forming the educational trail.

Marker seen along official segments of the Ice Age Trail

The goal of the Ice Age Trail Alliance, the organization that builds and maintains the trail, is to interpret the history of Wisconsin through the landscape.  They aim to complete the entire length of trail within the next 50 years, thus creating a protected space that anyone can utilize and appreciate.

For more information and a glossary of terms, visit the Ice Age Trail Alliance website at http://www.iceagetrail.org/.

To plan a hike: Contact the Ice Age Trail Alliance at (800) 227-0046 for help planning your hike.  An Atlas and a Companion Guide with information about each section of the trail are available.  Visit http://www.iceagetrail.org/plan-a-hike for guidelines, trail closings and further suggestions.

To volunteer: Volunteers logged over 65,000 hours last year maintaining the trails.  To learn more about volunteer opportunities, go to http://www.iceagetrail.org/become-a-volunteer or contact the UW Hoofers Outing Club (http://www.hooferouting.org/) and ask about their projects with the Ice Age Trail Alliance.

Listen Up…or Down or to the Side

We hear sounds around us every day, and usually we are able to find the direction from which the sounds come.  When hiking, a few notes of a bird’s song can lead us to locate the bird.  When walking down the street, someone calling our name causes us to turn in the direction of the caller.  How do we locate the source of a sound?

Let’s do a little experiment…  First, find a friend to help you.  As you sit in a chair with your eyes closed, have your friend shake a set of keys one of three places – above your head, at eye level, or near the ground.  After each shake, guess the location of the keys.  I bet you guessed correctly.  Now, push on the back of your ears, just above the lobes.  Push hard enough that you distort the shape of the ear canal but don’t completely block sound from reaching the ear.  Have your friend shake the keys in various locations again.  Did you guess correctly?  If you didn’t fare as well on the second part of the experiment, there is a good reason.

How do we hear and interpret the sounds coming into the ears?   It’s a question that Donata Oertel, professor and interim director of the Department of Physiology at the University of Wisconsin-Madison, has spent her career studying.  I sat down with Oertel in an attempt to understand this sense that many of us take for granted every day.

Oertel explains that when we hear sounds, we receive two important pieces of information – where the source of the sound is and what that sound means.  But the ear itself does not carry out these functions.

“From the signals that come from the ear, the brain has to extract the information it needs,” explains Oertel, “It turns out these are quite complicated computations.”

Our ears are far apart from each other on our heads for good reason.  When sounds come from the side, they will reach the near ear a little bit earlier than they reach the far ear.  If the sound is at a high frequency, it will also be louder in the near ear.

“These time and intensity differences sensed by the ear give our brains the cues to compute the location of the source of a sound in the horizontal plane,” says Oertel.  “But that process doesn’t help us determine where the sound is coming from in the vertical plane.”

Oertel explains that to locate a sound in the vertical plane, the asymmetry of our ears is important.  Our ears are asymmetrical, both top to bottom and front to back.  As sounds coming from various locations impinge on the ear at different angles, they interact with the ear differently and give the brain spectral cues.  The cues change as the elevation of the sound source changes, and we can then locate the source in the vertical plane.

Being able to hear a sound and locate the source is a great skill, but once a sound is heard, the brain must work to interpret it.  The question of how this happens was a new concept when Oertel began working in the auditory system, a field dominated by engineers in the late 1970s.

“Engineers described, where as I wanted to ask.  I wanted to ask why it was that these brain circuits were doing what they were doing,” says Oertel.

To find answers to the “why” questions, Oertel and her lab study the brains of mice.  Electrophysiological recordings can be taken from the part of the brain where the auditory nerves terminate, giving Oertel and her colleagues information about the neurons and how they are processing auditory messages.

Oertel’s hard work and knowledge of the brain have led to a number of interesting findings, including a circuit in the auditory pathway of the brain which Oertel believes functions to suppress echoes.  Sounds come directly from a source to our ears, but they also bounce off walls around us.  To accurately hear the sound and locate its source, we must suppress the echoes.

“I think one part of that ability comes from a brain circuit which receives a first excitation and then inhibits further signals,” explains Oertel.  “In this way, we can use the first signal but ignore the subsequent signals to accurately process the sound.”

So the next time you are walking through a crowd of people or trying to spot a bird you hear, stop and appreciate your ability to determine the direction from which sounds are coming.  And when a friend calls your name from through the crowd, be grateful you can pinpoint that person without calling for a search party.

The Costs of Alzheimer’s Disease

Alzheimer’s disease affects 5.3 million people in the United States, and it is the 7th leading cause of death.  In Wisconsin alone, 110,000 people currently live with Alzheimer’s.  Despite its prevalence, effective treatments and cures have yet to be found.  Due to the lack of therapies, those diagnosed with the disease often require long-term care, and Alzheimer’s care is a significant cost for patients, the state, and the country.

While older Americans make up about 12 percent of the population, they account for 90 percent of nursing home residents.  In 2010, Alzheimer’s costs reached $172 billion dollars.  Additionally, there are an estimated 10.9 million unpaid caregivers in the US providing around 12.5 billion hours of care.  This contribution was valued at almost $144 billion, $2.6 billion in Wisconsin alone.

Long-term care and other Alzheimer’s costs are paid by a variety of sources including Medicare and Medicaid.  In 2004, Medicare costs per Alzheimer’s patient ($15,145) were almost three times higher than costs for other Medicare recipients of the same age ($5,272).  That same year, 28 percent of Medicare recipients aged 65 or older also received Medicaid benefits.  Medicaid payments per Alzheimer’s patient ($6,605) were more than nine times higher than payments for other elderly people of the same age ($718).

Although Medicare, Medicaid, and other funding sources provide support for much of Alzheimer’s care, patients and families still must pay high out-of-pocket costs.  These costs include premiums, co-payments, and services that are not covered by other sources.  In 2004, out-of-pockets costs for Medicare recipients with Alzheimer’s averaged $2,464.  Average out-of-pocket costs for patients living in nursing homes or assisted living facilities were significantly higher at $16,689.

Another cost accrued by Alzheimer’s patients is hospice care.  The average length of stay for hospice patients with a diagnosis of Alzheimer’s was 105 days in 2008.  Total payments for hospice care from all sources totaled $2.8 billion in 2004 with per person payments averaging $976 (compared to $120 per person for patients without Alzheimer’s).

Because the costs of Alzheimer’s care is so high, and because the aging of the baby boomer generation is expected to greatly increase the number of Alzheimer’s patients, strategies for decreasing Alzheimer’s care costs is necessary.  This decrease could be achieved by shortening the disease course through earlier detection of the disease and more effective treatments.  With these improvements, treatments would slow cognitive decline, delay the age at which the disease appears, and increase the years that Alzheimer’s patients can remain at home.

In a 2009 paper, two Wisconsin researchers addressed this issue and calculated the potential cost savings if early detection and treatment of Alzheimer’s were possible.  Using a statistical analysis, the authors found that early detection and effective treatment of a 70-year-old woman with mild cognitive impairment would lead to $5,000 in state savings and  $10,000 in federal savings.  When a program of caregiver support was added to early detection and treatment, the analysis yielded even higher savings.  The authors stated that, by their calculations, the state savings were higher than the cost of implementing an early diagnosis program.  Therefore, if the state paid all costs of implementing an early detection and caregiver intervention program not covered by federal funds, the state would still save approximately $10,000 per diagnosed patient.

Currently, there is little incentive for caregiver support.  This paper concludes that the lack of support for family and friends is fiscally irresponsible.  With the development of caregiver support programs, patients could remain out of nursing home care for a longer period of time, thus significantly decreasing long-term care costs.

The high costs of Alzheimer’s care will continue to rise as people live longer and baby boomers approach the age at which Alzheimer’s is diagnosed.  In addition to the impact on Medicare and Medicaid spending, out-of-pocket costs put another stress on patients and caregivers.  With the current economic climate across the country, cuts in support for Alzheimer’s care may become necessary.

However, many studies are now focusing on the ability to detect and treat Alzheimer’s early, before cognitive decline can be measured.  Through earlier detection, more effective treatment, and additional support for caregivers, the costs of Alzheimer’s care for the state, the country, and families would decline.  Such a program would also provide hope and reassurance to those affected by a disease currently surrounded by uncertainty.

Data for this post provided by the Alzheimer’s Association.

Imaging Brain Changes in Alzheimer’s Disease

Alzheimer’s research aims to decrease some of the uncertainty surrounding causes, diagnosis, and treatment of the disease.  Many researchers believe that an important aspect of treatment will involve identifying the disease early and treating those early changes in the brain.

Beta-amyloid plaques are aggregates found in the brain of Alzheimer’s patients. Historically, these plaques were only identifiable upon autopsy.

A beta-amyloid plaque

Recently, better techniques for imaging these plaques have been developed.  As techniques improve, more information about the effects of the development of the disease on the brain can be gathered.

In a recent paper in Brain: A Journal of Neurology (published online February 9th), Gael Chetelat and colleagues use imaging techniques to more fully recognize early brain changes in Alzheimer’s progression and how those changes relate to memory decline.  Using magnetic resonance imaging (MRI), the researchers image and recognize a portion of the brain called grey matter.  They also use positron emission tomography (PET) to visualize a tracer that marks beta-amyloid deposits.  They aim to relate the breakdown of brain matter and the location of beta-amyloid plaques to the degree of memory loss in patients in the pre-dementia stage of Alzheimer’s disease.

The researchers find that memory performance of patients in the pre-dementia stage relates to two changes in the brain.  The first change is increased beta-amyloid deposition, specifically in the temporal neocortex.  The temporal neocortex is part of the outer layer of the brain located on either side, and it plays a critical role in visual processing, storage of language, and memory.

Labeling of temporal beta-amyloid deposition (left) and location of reduced grey matter in the hippocampus (right)

The second change in the brain is a decrease in grey matter in the hippocampus.  The hippocampus is located inside the brain structure with mirror-image halves in the right and left sides of the brain, and it is important in navigation and long-term memory.  The authors suggest that these insults to the brain structure should be considered separately as researchers look for possible targets of therapies.

The prospect of imaging specific changes in brain structure is exciting.  If these changes can be related to future Alzheimer’s progression or other forms of memory loss (which the authors caution cannot be done from their study), early identification of these insults may allow time for intervention and treatment that can slow or stop memory loss.  Knowledge of the specific locations of the insults as well as improvements in the techniques available to image the brain will be invaluable advances in the fight against dementia and Alzheimer’s.

Beta-amyloid photo here.  MRI photos from Chetelat study here.

A Personally Tested 30-Step Program to Become a Science Writer

1. Attend college intending to study science, but take a variety of interesting writing classes as well.

2. When it comes time to declare a major, decide that biology has more “promise” than writing or literature (because this is what your advisor tells you).

3. Take an expensive MCAT preparation class as you plan to enroll in an MD/PhD program.

4. After months of preparation, decide the MCAT and medical school are definitely not for you and take the GRE instead.

5. Apply to several graduate schools including Stanford.

6. Get a rejection letter from Stanford.

7. Get a second rejection letter from Stanford one week later.

8. Interview at University of Wisconsin – Madison.

9. Wonder if the fact that a large portion of your extended family lives within 20 miles of Madison is a deterrent to choosing that school.

10. Decide that the fact that a large portion of your extended family lives      within 20 miles of Madison is actually a draw to that school.

11. Attend the University of Wisconsin – Madison.

12. Enjoy your graduate classes during the first two years of your program as you realize you really like reading and learning about science.

13. Find a lab in which to do your research and begin a research project.

14. Outline several hypotheses about your project explaining why you may see the results that you see.

15. Perform experiments over the next several years that disprove each one of those hypotheses, one by one.

16. Realize at this point that the research you did as an undergraduate did not adequately prepare you for graduate work and that you may not be cut out for research after all.

17. After a series of experiments that are essentially fishing expeditions, fall upon an interesting result.

18. Recreate your project based on that interesting result.

19. Realize that even after getting an interesting result you still don’t feel cut out for research.

20. Begin to look into alternative career options you may have after completing your PhD program.

21. Continue working on your project that has now become centered on metabolism.

22. Find your college biochemistry book so that you can remember something about metabolism.

23. Attend career fairs and panels and strike gold as you listen to a science writer talk about her career.

24. Realize that you can read about, talk about and think about science without actually having to do the research yourself.

25. Do a happy dance.

26. Begin to apply to science writing programs as you continue experiments and begin to write your thesis.

27. Get accepted into science writing programs and decide to stay at Madison.  (Get no rejection letter from Stanford – but only because you didn’t apply there).

28. Finish and successfully defend your thesis.

29. Begin the science writing program and rediscover the fun of writing and reading about science when it doesn’t have to apply to your PhD project.

30. Start a blog on which you get to write the story of how you became a science writer.