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On Alzheimers Disease From Dr.Rudolph Tanzi

Hes professor of Neurology at Harvard Medical School and Director of the Massachusetts General Hospitals Genetic and Aging Unit. In the early 80s, Tanzi worked on an experiment that made disease genes identifiable. Since then, Tanzi has been on the forefront of Alzheimer research. His new book is called Decoding Darkness: The Search for the Genetic Causes of Alzheimers Disease (Perseus Books).

44:42

Other segments from the episode on January 29, 2001

Fresh Air with Terry Gross, January 29, 2001: Interview with Ridolph Tanzi; Review of the television series series, "Survivor: The Australian Outback."

Transcript

DATE January 29, 2001 ACCOUNT NUMBER N/A
TIME 12:00 Noon-1:00 PM AUDIENCE N/A
NETWORK NPR
PROGRAM Fresh Air

Interview: Dr. Rudolph Tanzi discusses the causes of Alzheimer's
disease and what researchers are doing to prevent it from occurring
TERRY GROSS, host:

This is FRESH AIR. I'm Terry Gross.

Today and tomorrow, we'll be talking with neurologists who are investigating
how the brain works by studying disorders of the brain. Today we talk about
memory and dementia with Dr. Rudolph Tanzi. He's been researching
Alzheimer's disease since the early '80s. He's helped identify three of the
genes that cause Alzheimer's disease and helped identify two other genes
believed to be related to Alzheimer's. Dr. Tanzi is a professor of neurology
at Harvard Medical School and director of the Massachusetts General Hospital's
Genetics and Aging Unit. With his co-author Anne Parson, he has written a new
book about the search for the genetic causes of Alzheimer's disease called
"Decoding Darkness." I asked him what he thinks causes Alzheimer's disease.

Dr. RUDOLPH TANZI (Harvard Medical School): Well, I think what we've learned
from the genetic findings in identifying the genes involved in this disease
over the last decade and a half is that no matter what the gene is--and
they're all very different from each other, or most of them are--is that
there's a common thread or a common consequence. And that is that as a result
of alterations in a variety of different genes, there's an accumulation in the
brain of a very sticky, you know, rather nasty substance we call beta-amyloid.
It's kind of an antiquated term, but we still use it. And this material, as
it accumulates, is thought to be toxic to nerve cells and to also cause an
inflammatory response in the brain, which is further detrimental to the
function of the neural circuitry that creates who we are.

GROSS: So it kills some brain cells and then prevents living brain cells from
communicating with each other?

Dr. TANZI: Yeah. The material is deposited outside of nerve cells, and
especially in the areas called the synapses, where the nerve cells make
contact with each other. So if you think about your brain as a big neural
circuit with, you know, billions of connections between nerve cells, this
substance starts to accumulate especially where you make these connections.
And so I guess the simplistic way to put it is it can create short-circuits in
the brain.

GROSS: Now there are also tangles in the brains of Alzheimer's patients. It
sounds almost like scrambled wires. Why don't you describe what those tangles
are?

Dr. TANZI: Well, the tangles are the second lesion you see in the brain of an
Alzheimer patient. And in fact, you know, to make a firm diagnosis of
Alzheimer's disease one would need to look in the brain and see a requisite
number of amyloid as plaques, and inside the nerve cells you would see these
twisted filaments called tangles. They almost look like twisted pretzels.
And so if you--you know, a nerve cell has a little skeleton of its own that
gives it its structure. It's called the cytoskeleton. And the proteins that
make up the skeleton of the nerve cell basically get really bungled up and
twisted around, and this looks like it's the signature of a dying nerve cell.
And the belief right now is that the amyloid comes first--and this material is
toxic to the nerve cells. And then as the nerve cells respond to this toxic
agent and they begin to die and, you know, they become dysfunctional you see
along the way in this process the tangles are forming made up of these
proteins that form the skeleton of the nerve cell.

GROSS: So are medical researchers working now on pharmaceutical drugs that
might be able to stop or slow the development of those beta-amyloids?

Dr. TANZI: Yes. The answer is yes. And the belief is that the best drugs
would be those that strike the disease at its earliest stages, right at the
roots of the disease. And the current thinking--and, you know, there's plenty
of data to support this--is that the amyloid is deposited first. And as the
nerve cells react badly to the amyloid, they start to form the tangles. So
although you might think, `Well, we could try to stop the tangles,' if that's
interfering with the nerve cell itself. If you want to get it earlier than
that, really nip-the-disease-in-the-bud stage, it's better to try to get rid
of the amyloid.

And so drug companies are thinking there are two ways to do this. And again,
it's the genes that have told us how to do this. You can either try to stop
the production of the amyloid or, on the other side of the coin, you can try
to promote its clearance and its breakdown. And ultimately, I think, the real
successful treatment for this disease will be, you know, a cocktail--let's
say--of drugs that stop do both: stop production and promote the breakdown in
clearance. And luckily, in the pipeline and in clinical trials, there are
drugs that do both of these things being tested right now.

GROSS: If you're just joining us, my guest is Dr. Rudolph Tanzi. He's a
professor of neurology at Harvard Medical School, author of the book "Decoding
Darkness: The Search for the Genetic Causes of Alzheimer's Disease." And
he's a scientist who's helped identify three of the genes associated with
Alzheimer's disease, and he's working on two others believed to be associated
with the disease.

You have been involved in identifying five genes that are related to
Alzheimer's disease. Do they each function in a different way in creating
Alzheimer's?

Dr. TANZI: Well, it's interesting. You know, if you look at the genetics of
Alzheimer's disease, there's a real polarization in that the genetics is very
different for the very early onset cases that strike under 50 or under 60
years old vs. those that influence the most common form of the disease that
strikes after 60. And I should say, just for the sake of numbers, that about
5 percent of Alzheimer's can occur under 60 years old and only 1 percent under
50. You know, the vast majority of it occurs after 60 years old.

And what we see is that the earlier the disease strikes in life, the more
profound and the more robust the role of genetics is. So the first three
genes that I was involved with in terms of my studies were all the early onset
genes. And what they have in common is that they contain very rare mutations
that only account for maybe 1 or 2 percent of all cases of Alzheimer's. But
these mutations can teach us a lot about the disease in general because when
they're inherited they cause the disease, with virtual certainty--in other
words, it's almost 100 percent certain that one will get the disease when they
inherit these rare, early onset Alzheimer gene mutations, as we call them. In
the late onset genes, so far, we just see an influence towards susceptibility
and increased risk.

GROSS: What else are you learning about the disease and how it's created by
learning about the genes?

Dr. TANZI: It's very interesting. It's amazing how things are falling into
place. You know, as we age, all of us are accumulating this material called
amyloid in the brain, just like we accumulate cholesterol in our blood
vessels. And how much we actually in the end accumulate in various regions of
the brain depends on production vs. clearance and breakdown. It's a formula
of balance. So if you produce too much, you're in trouble--and that's with
the early onset genes. If you break it down too slowly, you're in trouble.
And that seems to be the input of the late onset genes. So from a drug
standpoint, you would like to try and lower production the way the early onset
genes have taught us to do, and you'd like to also promote the breakdown in
the clearance of the material the way the late onset Alzheimer genes are
teaching us. So it's really quite a neat formula, and luckily these drugs are
now in clinical trials. In the last chapter of our book, we actually go into
detail about some of the more exciting clinical trials that are being driven
by these really wonderful genetic findings that have occurred over the last
decade or so.

GROSS: Now when you mentioned that everybody starts producing these sticky,
nasty beta-amyloids, I think I heard a lot of our listeners go, `Oh, no,'
because so many people--particularly people in their 40s and up--fear that
they're losing their memory, that they can't remember things as well as they
used to and they worry, `Is this, like, early onset of Alzheimer's disease?'
If you're feeling like you're not remembering things the way you once did, or
words aren't appearing in your mind the way they once did, does this mean that
you have beta-amyloids building up in your brain?

Dr. TANZI: That's an excellent question. And I think the best way to answer
that is to suggest, for simplicity, three different types of memory problem.
First is just forgetfulness that comes with age. This probably has nothing to
do with amyloid or tangles or anything we see in Alzheimer's. Remember, the
brain is a neural circuit. Its connections--billions of connections between,
you know, billions of nerve cells. And just like, you know, a piece of
electronic equipment, with age that circuitry begins to deteriorate a bit, and
forgetfulness can occur naturally.

On the other hand, all of us as we age--and especially after 40--are starting
to accumulate some of these lesions you see in Alzheimer's. They are a fact
of life; the amyloid plaques and the tangles you see inside the nerve cells.
But these lesions have to reach a certain level before they start to threaten
your actual quality of life, where loss of memory and cognitive decline starts
to threaten your everyday functioning. At that point, you get into the second
level of memory loss, which we call mild cognitive impairment, or MCI. And
this can go either way. It can be, you know, just a very severe case of
forgetfulness that comes with age and never proceed to Alzheimer's. But
certain cases of MCI can also proceed to full-blown Alzheimer's. And when you
do see full-blown Alzheimer's as, you know, determined by cognitive testing or
in some cases helped by imaging studies of the brain, at this point the
lesions involving amyloid tangles have reached such a tremendous level in
areas of the brain involved in learning and association that now they threaten
the quality of life and everyday functioning of the brain. At this point you
can say it's now in the early stages of Alzheimer's disease. But the bottom
line is for just forgetfulness that occurs after 40 years old, do not panic
that it's Alzheimer's disease. It's natural.

GROSS: My guest is Dr. Rudolph Tanzi. He's been researching the genetic
causes of Alzheimer's disease since the early '80s. He's the co-author of the
new book "Decoding Darkness." More after a break. This is FRESH AIR.

(Soundbite of music)

GROSS: My guest is Dr. Rudolph Tanzi. He's a professor of neurology at the
Harvard Medical School and the author of the new book "Decoding Darkness: The
Search for the Genetic Causes of Alzheimer's Disease." He's the scientist who
has helped identify three of the genes associated with Alzheimer's disease and
is working on two others believed to be associated with the disease.

Dr. Tanzi, what are your thoughts on genetic testing now? Do you feel that
someone who has reason to believe that they might be prone to Alzheimer's
disease should get the genetic testing?

Dr. TANZI: Well, right now there really is no feasible way to do reliable
genetic testing for the most common form of Alzheimer's that strikes after 60
years old. For the early onset genes that we and others have identified that
carry mutations causing the disease under 60, it's possible to do testing, and
that's only about 1 to 2 percent of cases. So it's not very applicable to the
disease in general.

But for the late-onset, you know, common form of this disease that accounts
for, you know, greater than 95 percent of cases, we don't have a reliable gene
test yet. I do believe that current research is moving at such a frenetic
pace that we will have a whole set of genes that are confirmed for late onset
beyond the one that's most established already, so that we can combine those
genes together into a test to assess one's overall risk for getting the
disease at a certain age.

But caveats come to mind. For example, is it worth doing this type of test if
there's nothing you can do about the disease, that there's no drug out there
once a positive outcome is found? What about the family of the patient?
They're going to worry quite a bit if a family member carries these genes.
They'll worry about their own well-being and again you're going to want to
offer some form of prevention for them.

And I think one of the most important aspects to bring up is protection
against discrimination according to one's own genome. You know, right now
we're making strides toward genetic privacy and protecting individuals against
genetic discrimination, but we're not there yet and I think we really have to
have a very firm stand in this country and other countries to say that no one
can be discriminated against by health insurance companies, employers or
otherwise simply because of the DNA in their genome. And until we reach that
stage, we're going to have to be very careful with genetic testing.

And it's important to do that because in the future, treatment of diseases
like Alzheimer's and other diseases that are age-related, like cancer and
diabetes and heart disease, are going to require early prevention. You need
to really attack these diseases at their root stages before they take hold and
that means early prediction, using genetics, and then early prevention. We
can't do that until protection against discrimination is firmly established in
our government and our medical systems.

GROSS: If you have a parent or a grandparent who has had Alzheimer's disease,
does that necessarily mean that you're more likely to get it?

Dr. TANZI: Well, again, there's a spectrum there for early- vs. late-onset
disease. If one has a parent or a grandparent who got Alzheimer's disease
under 50 years old, and that's pretty rare, the genetic component's pretty
strong. Unfortunately there, there is reason to be concerned, because if a
parent had one of these causative mutations that we've seen in the early-onset
genes, there's a 50:50 chance of passing it down to the children. And that's
certainly a concern for cases that occur under 50.

Under 60--or let's say between 50 and 60, you enter a gray area where it could
be this very strong genetic component with a 50:50 chance of causation or it
could tend toward the late-onset Alzheimer's situation in which, you know, for
the vast majority of the cases that occur in the 70s or 80s, genetics plays a
role, but it's just susceptibility. There, even if you inherit the gene or
genes from a parent that caused their risk for Alzheimer's, it's not a given,
it's certainly not a guarantee you're going to get the disease. So it really
is quite different for one's situation if they have a family member with
early-onset Alzheimer's disease, especially under 50, vs. common garden
variety Alzheimer's, so to speak, that strikes in the 70s or 80s or later.

GROSS: Are there things you are learning about memory and how memory
functions, from studying Alzheimer's?

Dr. TANZI: You know, when I first started studying Alzheimer's back in the
'80s, I thought that was going to be the case. I thought that the genes we'd
come up with and the biological pathways we would see would be directly
involved with, you know, the secrets to memory, you know. But, surprisingly,
I'd have to say so far that hasn't really been the case. Most of the genes
that have come up and even the genes that continue to crop up really affect
more the rate of accumulation of amyloid in the brain, just this toxic invader
that, you know, is made by nerve cells and accumulates outside the nerve cells
and attacks the neurocircuitry. We have not yet seen so far from genetics
genes that, you know, delve into the mysteries of memory affecting this
disease. It looks more like a pretty direct attack of a nasty substance, what
we call amyloid.

GROSS: Why is it then that most people who have forms of dementia seem to
lose their long-term memory last and their short-term memory first?

Dr. TANZI: Well, because it looks like in the earliest stages of the disease,
the parts of the brain that are involved with registering short-term memory,
areas of the brain like the hippocampus, coming from the Latin for sea horse,
because it's a little area of the brain that looks like a sea horse. And
there's another area that feeds the hippocampus information, so as your
sensory organs, you know, take in information--your eyes, your ears, your
nose--it goes through another area called the inter-rhinal cortex and that's
like a little transfer station that then sends that information to the
hippocampus, you know, you just smelled an apple, register that in the
hippocampus as memory. Well, that connection between the inter-rhinal cortex
and the hippocampus seems to get severed very early in the disease. This was
one of the early findings in the mid-80s. And the reason for that is not
exactly clear, but we do know that the pathological lesions, the amyloid and
the tangles, do seem to concentrate in these areas of the brain like the
hippocampus, like the inter-rhinal cortex, that's directly involved with
short-term memory and registering sensory information that comes in on, you
know, a minute-to-minute basis.

GROSS: You explained a bit about why short-term memory is usually the first
thing to go with Alzheimer's disease. Is there more of a progression that you
usually see?

Dr. TANZI: Well, it begins with short-term memory and eventually, as, you
know, various parts of the brain begin to get affected, Alzheimer's will
eventually affect long-term memory and then eventually could even effect parts
of the brain involving movement, so you'll sometimes see in the very late
stages, you know, Parkinsons-like symptoms as well. So it progresses out from
short term to long term to even movement types of problems in the patient.
But I think, you know, in terms of thinking about drugs, we have to
concentrate on where the genes tell us to concentrate, and that is that the
earliest stages of this disease are in the areas of the brain more involved
with short-term memory, you know, minute-to-minute associations and if we can,
you know, nip the disease in the bud stage by not letting the lesions occur in
these various early regions of the brain that are affected, if we use genes to
guide us in how to do that, you know, I'm very optimistic that we will have
drugs within, let's say, five to 10 years which will be effective.

The development of these drugs is converging in parallel very nicely with our
understanding of the genetics and our identification of the genes involved
with the disease; most importantly, the genes involved with the most common
late-onset forms of Alzheimer's that strike in the 70s or 80s. So eventually
what we would hope to have is a genetic test that can be performed
confidentially and with protection, with proper counseling, genetic
counseling, psychological counseling for the patient and families and then
combine that genetic testing with prescribing just the right cocktail of drugs
that's best for that individual based on their own genome. That includes
drugs that would be the safest in those individuals, again based on what the
genome testing tells the doctor.

GROSS: Dr. Rudolph Tanzi is the co-author of "Decoding Darkness: The Search
for the Genetic Causes of Alzheimer's Disease." He's a professor of neurology
at Harvard Medical School. He'll be back in the second half of the show.

I'm Terry Gross and this is FRESH AIR.

(Announcements)

GROSS: Coming up, we continue our conversation about the causes of
Alzheimer's disease with Dr. Rudolph Tanzi. After studying the disease for
years, his own grandmother developed Alzheimer's. Also David Bianculli
reviews the season premiere of "Survivor 2."

(Soundbite of music)

GROSS: This is FRESH AIR. I'm Terry Gross, back with Dr. Rudolph Tanzi.
He's been researching the genetic causes of Alzheimer's disease since the
early '80s. He helped identify three of the genes that cause the disease and
two others believed to be related. He's the co-author of the new book
"Decoding Darkness: The Search for the Genetic Causes of Alzheimer's
Disease." Dr. Tanzi is a professor of neurology at Harvard Medical School and
director of the Massachusetts General Hospital's Genetics and Aging Unit.

Dr. Tanzi, during the course of your research, your grandmother developed
Alzheimer's disease. Are there things that you started to understand about
the disease on a different level from actually seeing her?

Dr. TANZI: In the case of my grandmother, it's very interesting because we
need to consider the risk factors for Alzheimer's disease in which the number
one risk factor is age; number two is family history, and that's where the
genetics comes into play; number three is gender, women do get it more than
men, even after, you know, correcting for the fact that women live longer than
men; and number four is head trauma, and I think that one was most pertinent
to my grandmother because she had quite a fall early in life, when she was in
her 50s, in which she banged up her head quite badly and needed stitches.

And, you know, one thought is that you have really an interplay between
genetics and environment from many age-related disorders, whether they be
Alzheimer's or heart disease or diabetes. So in my grandmother's case, I
think what might have happened is that she was genetically predisposed to the
disease and may have escaped it, you know, but was--the disease could have
been triggered by the head trauma, you know, quite severe head trauma, that
she suffered when she was in her 50s. So it taught me that, you know, it's
really important in the future to also identify more of the factors of life
exposure and environment in addition to genetic factors, all of which can
conspire to cause risk for the disease.

On the more personal level, I would say that it was absolutely terrifying to
see that her--the changes in my grandmother were not typical to Alzheimer's.
It wasn't simply memory loss, and this may have to do with the fact that it
started with head trauma, but she went from being a very sweet, kind,
generous, you know, elderly woman who, you know, made me homemade pasta and
held me in her lap when I was a kid to being quite scared, aggressive,
paranoid. I mean, it was a different person. She didn't just lose her
memory, lose herself, her personality dramatically changed into someone who,
you know, I had no idea who she was anymore.

GROSS: Have you come across that much in people who didn't suffer severe head
trauma before the onset of Alzheimer's, that kind of personality change?

Dr. TANZI: Well, it's interesting because in Alzheimer's, you know, the
personality change can occur, but usually it's out of frustration, because of
memory loss and just, you know, not being able to find the right words. There
is, however, another form of dementia that I think is underappreciated that is
not Alzheimer's disease, but we call it FTD for frontal temporal dementia.
And in this other form of dementia--and, you know, one form of frontal
temporal dementia, for example, is Picks disease, which people may have heard
of. You can also get dementia with Parkinson's symptoms due to these
mutations. And in this case, some of the earliest signs are not necessarily,
you know, memory loss, but severe personality change. And it is quite a
different disease, although the pathology is shared with Alzheimer's with
regard to tangles, at least in a percentage of the cases.

GROSS: Now I know most of your research is in the laboratory, but do you do
research with people who actually have Alzheimer's disease, research in
observing them or doing any medical research with them?

Dr. TANZI: Well, you know, I run a lab--actually a research unit where we do
experiments in the realm of molecular biology, cell biology, biochemistry.
But I am performing genetic studies on, you know, well over 5 or 600 families
for the purposes of observing the patients and following the course of their
disease or following siblings to see who--you know, that may be at risk. I
have very good collaborators who do that type of testing and do the clinical
assessment outside of my laboratory, and then keep that information actually,
you know, in many cases, blinded from me because, you know, I provide, you
know, the genetic data and, you know, in true scientific fashion we try to do
this as blindly as possible also for confidentiality. You know, I prefer not
to know the names of the families I'm working on, and for their protection as
well, you know. I don't want to, you know, be in any situation where I have
to, you know, suddenly give out their genetic information. So we keep the
clinical assessment side separate and blinded from the genetic testing side
for a variety of reasons.

GROSS: You didn't initially set out to study Alzheimer's disease. You were
studying Huntington's disease and Down syndrome. How did that lead you to
Alzheimer's?

Dr. TANZI: Well, in the early '80s I had--you know, I was just really lucky.
Out of college, I hooked up with Professor Gassella, Jim Gassella(ph). At the
time, I was 21, he was 26. And there was no Human Genome yet. You know,
you--I mean, there was a human genome, there was no Human Genome Project yet.
You know, there were very few genes known. And Jim Gassella had this idea
that, hey, you could go and try to find the gene responsible for a disease
simply and only using genetics without having to really know anything about
what goes wrong in the brain in that disease, just the power of genetics to
get you there. And many people thought this was crazy. And we were very
lucky 'cause Jim's idea worked out. And, in fact, the Huntington's disease
gene, when it was localized in the early '80s, was really the first disease
gene to be found where we had no prior ideas about the chromosome involved or
the proteins involved or anything like that, just straight genetics, looking
at the families and testing, you know, markers inside of the genome, DNA
markers as we call them.

Around the same time, muscular dystrophy was being worked on, but there, they
already knew, based on the sex-linked nature of that disease with males vs.
females, that it was probably on the X chromosome. But the first disease gene
to be found where it could've been anywhere in the genome using only genetics
was Huntington's. And, you know, I was the hands at the bench, you know, for
Jim that did the work and it was a great way to be introduced into a
revolutionary field.

So I decided, while working with Jim and about to become a graduate student in
neurobiology at Harvard, that in anticipation of that, that I wanted to try to
build a map of a chromosome, you know, a kind of a pre--you know--Human Genome
Project chromosomal map. And I chose the smallest one. Frankly, I thought I
could finish it fastest if it was the smallest chromosome, and the smallest
chromosome is number 21, and that's the one that's involved in Down syndrome,
where Down syndrome patients have an extra copy of that chromosome in every
cell. And when I had learned, and I should say others had learned as well,
that Down syndrome patients, when they reach middle age, start to accumulate a
vast amount of the Alzheimer pathology that you see in Alzheimer patients, I
and other labs as well speculated that there may be an Alzheimer's gene on
chromosome number 21. And again, I was in a very lucky position because I was
sitting there with the genetic map of chromosome 21 that I had helped to
construct.

So I really landed into Alzheimer's by picking the right chromosome to work on
in a very early, you know, pre-Human Genome Project era, you know, small
project in Jim Gassella's lab. And then once I started on Alzheimer's and
things started to work out, I never looked back.

GROSS: My guest is Dr. Rudolph Tanzi. He's been researching the genetic
causes of Alzheimer's disease since the early '80s. He's the co-author of the
new book "Decoding Darkness." We'll talk more after a break. This is FRESH
AIR.

(Soundbite of music)

GROSS: If you're just joining us, my guest is Dr. Rudolph Tanzi. He's a
professor of neurology at Harvard Medical School and author of the new book
"Decoding Darkness: The Search for the Genetic Causes of Alzheimer's
Disease." He's a scientist who has helped discover three of the genes that
are involved in Alzheimer's disease and he's discovered two of the other genes
believed to be associated with Alzheimer's.

I'm going to ask you to look ahead a little bit for us. If you look ahead,
say, 10 or 20 years, optimistically but not in too phony a way, what are some
of the possibilities you see for the prevention or treatment of Alzheimer's?

Dr. TANZI: Well, I think there's a very good chance--and I must say I'm very
optimistic about this--that five to 10 years from now--and I don't know if
it's five years; maybe it will be 10 years, but sometime over the next decade,
we will see a real masterful convergence of drug development and I think the
amyloid hypothesis is going to win. I think it will be drugs that curb the
production of amyloid and help break it down in the brain. These will be
developed coming out of clinical trials, ready to go, the same time we're
going to have probably anywhere from five, maybe more--maybe five to 10 both
major and minor genes that influence the risk for Alzheimer's disease. And
one can be tested around, let's say, 40 years old for their overall risk for
the disease, and again, assuming this can be done legally and confidentially
without discrimination, and that gene profile would then allow a physician to
guide this person into a preventative treatment for the disease based on what
this own genome tells the doctor.

So now we enter in a bit of a quagmire because one must ask, well, jeez, you
know, all of us--this is a common age-related disorder. I mean, Alzheimer's
is striking up to 40 percent of individuals over 85 years old. Can HMOs and
can health insurance afford to give everyone preventative treatment for
potentially expensive drugs starting at 40 years old and assuming that they
might be on those drugs for 40 or 50 years? You know, who is eligible, who is
not? So there we're going to get to a real gray area of, when does the
genetic profile say that preventative treatment is justified starting at an
early age?

Now I'm looking, you know, years ahead here, but I think we're going to see
great debates five or 10 years from now about just when genetics justifies
that a health insurance company should pay for a potentially expensive drug
for decades of treatment to prevent an age-related disorder. And this isn't
only for Alzheimer's. We're going to see this for all of the major
health-related, age-related diseases from Alzheimer's to heart disease to
diabetes to various forms of cancer

GROSS: Your grandmother had Alzheimer's disease. Do you worry about getting
it yourself? Do you want to get yourself genetically tested, even though
there's really nothing you could do about it if you found that you were
genetically prone to it?

Dr. TANZI: I decided that over the next decade, when genetic testing is
reliable--and I emphasize it is not at all reliable right now for the most
common form of this disease--that when reliable testing is available, if there
are drugs, even one drug that can help lower the chances of the disease taking
root and help prevent the disease, yes, I would want the test and I would like
to get on that drug and I would, you know, pray that my health insurance
covers such a drug, given my genetic profile. But I would not want to be
tested personally until there was a drug available to do something about it.
Now everybody is different. I mean, everybody, you know, is going to have to
make their own choice. Some people might want to know, even if there's
nothing you can do about it. It's a very personal decision.

GROSS: What kind of medications, if any, are available now for people with
Alzheimer's?

Dr. TANZI: Right now there's a class of drug that's called the cholinesterase
inhibitor. So what is that? Well, one of the chemicals in your brain, a
neurochemical, that is needed for learning and memory and association is a
chemical called acetylcholine, which is a neurotransmitter. One nerve cell
sends it to another nerve cell as a chemical to say, `Here's a signal, here's
a message for a memory, for an association.' It ends up that in Alzheimer's
disease, although many different nerve cells are attacked, many different
neurotransmitters and neurochemicals are depleted, one in particular that we
really need for memory is acetylcholine. So it was decided, you know, long
ago, based on those findings that started in the '70s, maybe we should try to
preserve the amount of acetylcholine in the brains of patients.

Now what breaks down that neurotransmitter is a certain enzyme and the class
of drug that's out there right now is one that tries to inhibit that enzyme
from breaking down acetylcholine so you have more of this neurotransmitter
around, you know, for when you need it for learning and memory. So you
basically try to preserve the neurotransmitter by preventing its breakdown.
The drugs that do this--two of the best examples are Aricept and
Exelon, and I think both of them work, you know, pretty much comparably.
Problem is, you know, they only treat a symptom. They're treating a memory
symptom. They're not getting to the roots of the disease. They're not
stopping the amyloid, they're not getting rid of the tangles.

And another problem is that even with the positive effect of these drugs,
sometimes the effect can wear off after a few months and the patient is back
to square one. But, you know, they're better than nothing, and at least
there's something out there that one can take and have a bit of hope, even
though, as I think about it, you know, they amount to a Band-Aid on a pretty
gaping wound.

The other treatment is simply vitamin E because as things start to go downhill
in the brain and amyloid accumulates and nerve cells are lost, there's what's
called an inflammatory response in the brain and free radicals are produced.
And these little--you know, they're like little tiny bullets that are made in
the brain as part of an inflammation response. And so these free radicals,
even though the brain is making them deliberately because they think they have
to kill something off that's attacking the brain, for example, if you've got
bacterial meningitis, the way the brain kills that bacteria in the brain is
there's an inflammation and free radicals are made like little bullets to kill
the bacteria.

But in this case, there's no bacteria. There's amyloid and there's dying
nerve cells, so these free radicals can ironically turn on the brain with
friendly fire and kill even more nerve cells than what were originally
attacked. So you want to try to curb that inflammatory response a bit so
aspirin and ibuprofen have been proposed as potentially useful. And there
again, you have to worry about, you know, GI tract complications, ulcers, you
know, that kind of thing. And vitamin E, which is an antioxidant, has been
proposed because it can help reduce the number of free radicals in the brain.
And it appears that vitamin E--you know, there are trials going on right now
for the combination of vitamin E plus Aricept or Exelon, and you know, the
thought is that the combination is probably a good idea for now, given that we
really have nothing else. There are also trials looking at anti-inflammatory
drugs. And so that's really all we have right now.

GROSS: So many people I know feel that they want to find a certain word and
they just can't find the name for something they're looking for, the name of
the thing they're looking for. Or they just kind of forget what it is they
were gonna say. You know, just like absentmindedness. Do those sound like
serious symptoms to you or like typical signs of getting a little bit older?

Dr. TANZI: It really depends on how often that happens and whether it's
starting to severely affect your own quality of life and your own everyday
activities at your job or at home. You know, I'm 42, and I forget all the
time, you know, why I went into the living room or why I left my office to go
to the lab, and you know, I forget words. I forget names. It's natural, it
comes with age. It happens especially after 40 years old, you know, there's
nothing you can do about it. But if it starts becoming so severe that, you
know, every five minutes there's a word you can't remember, a name you can't
remember, you're constantly forgetting, you know, why you got up out of your
seat to go into the kitchen. You know, it's really frequency. If it happens
very, very often to the point that you're becoming frustrated and saying,
`Jeez, I can't live a normal life anymore,' then it's time to see the doctor.
Otherwise, I think the rule is, you know, not to panic and not to assume for
the worst.

GROSS: One last question. It sounds to me that you must be pretty constantly
excited by the work that you're doing.

Dr. TANZI: I'm overwhelmingly excited about the work I'm doing. I, you know,
and not just me. I think, you know, and I have to say that, you know, in
"Decoding Darkness," what we try to celebrate is an incredible chapter in the
history of medical research where 20 years ago, we really knew nothing about
this disease except these lesions that accumulate in the brain that Dr.
Alzheimer himself saw in a patient in 1906. For the entire century, we went
on just knowing that when you look at the brain of an Alzheimer patient after
autopsy, you see these lesions. Trying to figure out the disease before the
age of genetics was like going to Foxboro stadium--I mean, I'm a Patriots fan
despite the season, and trying to figure out the game of football, you know,
two hours after the game ended, you know, looking at the stands and the litter
and the dug-up dirt. Maybe you might find a page torn out of the playbook or
a Gatorade cup, but you're not gonna understand the game of football.

But the work of really, you know, hundreds if not thousands of labs around the
world, dedicated researchers have really, in 20 years, turned this around in
that we've been able to identify the genes and from there identify what goes
wrong with them, which biological pathways are being abnormally altered and
now the ideas for where to target drugs come around. And so I think it's
really one of the most, if not the most exciting fields of medical research to
be in today.

GROSS: Well, Dr. Tanzi, thank you so much for sharing some of your research
with us.

Dr. TANZI: You're very welcome. Thank you very much.

GROSS: Dr. Rudolph Tanzi is the co-author of "Decoding Darkness: The Search
for the Genetic Causes of Alzheimer's Disease." He's a professor of neurology
at Harvard Medical School.

Coming up, TV critic David Bianculli reviews "Survivor 2." This is FRESH
AIR.

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

Review: New CBS series, "Survivor: The Australian Outback"
TERRY GROSS, host:

Last night after the Super Bowl ended, CBS presented the first installment of
its sequel to "Survivor," last season's smash-hit series. Its regular spot
will be Thursdays opposite NBC's sitcom, "Friends." TV critic David Bianculli
has this review.

DAVID BIANCULLI:

Was CBS smart to schedule "Survivor" after Super Bowl XXXV? Let me answer
that question by asking another. This morning, at the office or at home, what
were you talking about the most? Was it that thrilling final quarter of Super
Bowl XXXV? Or all those spectacular commercials, most of which faded from
memory as soon as they faded to black? Or was it "Survivor: The Australian
Outback" with its granite waterfall, its vomit bags and its bug-infested figs?

That's what I thought. Any doubts about whether this new "Survivor" would
match its South Seas predecessor in terms of personality conflicts and
breathtaking scenery were erased almost instantly. Last time, the show's
premise, the rules and the true strategic importance of the immunity
challenges were brand new. This time, the audience, like the more buff
contestants this time around, know exactly what to expect and what is at
stake. It's still 16 people competing and scheming to be the last one playing
the game and grab that million-dollar prize. It still begins with the
contestants divided into two tribes of eight competing against one another for
goodies, like waterproof matches and for immunity, which means the other tribe
has to throw someone out of the outback.

In this new "Survivor" series, the two tribes are called the Kucha and the
Ogakor. The Ogakor won the challenge last night, but the Kucha had all the
best TV moments. Jeff got sick and threw up early, just like Ramona had in
the original "Survivor." Last time, Rudy, Rich and B.B. were the most
irritating people out of the gate. In Australia, the early irritants were all
Kuchas. There was Mike, the pushy leader when it came to building a shelter;
and Debb, an equally vocal corrections officer who was the first to be voted
off, making her this year's Sonja. And finally, there was Kimmi, the
loudest and most abrasive person caught by the "Survivor" night vision cameras
the tribe's first evening in their cramped little shelter.

The next morning Debb and Jeff had something to say about her.

(Soundbite of "Survivor: The Australian Outback")

Unidentified Man #1: You got to share something about yourself that's really
embarrassing.

KIMMI: OK. I just got naked in a tent with a bunch of strangers.

JEFF: That's what I was getting ready to say.

Unidentified Woman: Give us the dirt, girl.

Unidentified Man #1: Ex-boyfriend, husband, wife, you know...

KIMMI: OK, A, not married; don't believe in marriage until I'm 35.

Unidentified Woman: OK, don't say you're a virgin 'cause I swear to God,
I'll...

KIMMI: My main concern was where in the hell am I gonna masturbate out here?

(Soundbite of laughter and unintelligible comments)

JEFF: You have got to be kidding me!

(Soundbite of interview)

DEBB: Kimmi is a happy-go-lucky person who's got, I don't even know how to
describe her. I don't know what the right word is. She--nothing is taboo
with her, nothing at all.

(Soundbite of "Survivor: The Australian Outback")

KIMMI: Listen to me. You guys might like a skin, however, on occasion...

(Soundbite of interview)

JEFF: Kimmi will not shut up. You know, I'm tired at night, I want to go to
sleep. And they're constantly talking. And with the headache that I have,
it just reverberates. Kimmi cannot say a single thing without screaming it.

(Soundbite of "Survivor: The Australian Outback")

KIMMI: All right. Someone just stuck their finger in my (censored).

Unidentified Woman: Well, it was on my head.

(Soundbite of interview)

JEFF: All of a sudden, out of the blue, with that accent, she talks and
talks and talks and talks and talks--I just want to grab her by the neck and
shake the (censored) out of her, you know?

(Soundbite of "Survivor: The Australian Outback")

KIMMI: Oh, my God, I love you...

BIANCULLI: Host Jeff Probst, handling the first tribal council, seemed to be
having fun from the start, even if the contestants didn't. As for the scenery
this time, it was beautiful. The overwhelmingly clear night sky, the granite
waterfall on which the tribal councils are held, and the riverside camp
settings are all major pluses. Last night's premier even had one of those
wonderful "Survivor" surprises. A bite into a wild fig resulted in the
discovery, not of an exotic Australian delicacy, but of a fruit fully infested
with tiny bugs.

This "Survivor" like the last one, is shaped and presented like a true mystery
story. It's the production values, editing and character development that
make it so appealing. It also promises an ultimate finite conclusion, making
it very unusual in TV dramatic terms. "Survivor," in a way, is the modern
equivalent of those sweeping miniseries we used to flock to 20 and 25 years
ago. We end up caring about these characters, but not all of them make it to
the end. And unlike weekly TV dramas that seem to go on forever, there is an
end to "Survivor."

In terms of network competition, though, this is only the beginning. In three
days, "Survivor" goes up against "Friends," and NBC is taking that threat so
seriously that the network is countering by adding 10 minutes to "Friends," at
least for the first few weeks, and presenting special live mini installments
of "Saturday Night Live." The "Friends" expansion, that's no big deal. If
NBC had a better comedy than the "Weber" show after "Friends" it'd probably
stand pat. The "Saturday Night Live" move is much smarter. It'll promote the
late-night show in prime time, and like "Survivor," offers something that
people are likely to talk about the next morning.

But what "Survivor" has as its hold card is momentum. Each show becomes more
dramatic and more important as the contestant pool is pared down. Last season
the audience levels kept growing and the climax of the South Seas "Survivor"
was one of last season's most popular TV programs, second only to the Super
Bowl.

Now answer these last two questions as quickly as you can. Number one, who
won last year's Super Bowl? Time's up. Now here's question number two, who
won last year's "Survivor"? I rest my case. Trust me, folks, no matter what
NBC or any other network throws against it, "Survivor" isn't going anywhere
for a while.

GROSS: David Bianculli is TV critic for the New York Daily News.

(Credits)

GROSS: I'm Terry Gross.
Transcripts are created on a rush deadline, and accuracy and availability may vary. This text may not be in its final form and may be updated or revised in the future. Please be aware that the authoritative record of Fresh Air interviews and reviews are the audio recordings of each segment.

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