Ayaka Ohara

IR-2/11AP
December 9th, 2017

Interview
Interviewee: Regina Leckie
Workplace: University of Pittsburgh
Title: Postdoctoral Fellow
Date of the interview: December 1, 2017

AO: Hello, is this Dr. Regina Leckie? This is Ayaka Ohara.

RL: Hello. Yes this is. How are you doing?

AO: Great! How are you?

RL: Good as well. I apologize for the inconvenience a couple days ago. As I said in
the email, my daughter had the stomach flu.

AO: It is no problem.

RL: So, how do you want to do this interview?

AO: Basically, what I’m suppose to do is ask you a couple questions, and since you are
my advisor, you can also help with the direction that I would go with my research
process.

RL: Absolutely.

AO: I’ve been reading a lot of articles lately that have to do with the different
nutritions, and I’ve kind of been narrowing it down to things like saturated fats,
antioxidants, and Omega 3 fatty acids. I’ve also seen some about of the coppers
and aluminum, but I don’t know if I should go down that route or not.

RL: So, a lot of metals are more difficult. There’s more conflicting literature on that,
and a lot of it is also more post-mortem. So, I would say your best bet in terms of
amount of literature that’s out there is going to be Omega 3. There is a massive
body of work there. Antioxidants are more conflicted, so you have smaller
insecticides with things like the accaratin, retenal, accatocafarrel, betacricithanin.
So, those are antioxidants, basically, Vitamin A, Vitamin E, B6, and B12. So,
 there’s literature on those that would be interesting and would be helpful in terms
of an overall diet, but the effects are much smaller than what you would typically
see in Omega 3. For how saturated fats go, that’s a little more difficult, because
those are from diet questionnaires. So, i’m assuming a lot of what you have been
reading has been coming from block questionnaires, and what they will do is, they
will give someone a diary and say list everything you’ve ate in the last week. And
people have to make up portion sizes and guess a lot if they forget things or
intentionally leave stuff out because they don’t want to admit that they’ve ate
something. And then a nutritionist will go in and actually score those foods and
the written portion sizes, so there’s a lot of human error involved in those. I would
stick to things that say serum levels or circulating levels cause that insinuate that
there was blood drop.

AO: So, going back to Omega 3 fatty acids, I’ve read that, doesn’t it contain the
docosahexaenoic acid?

RL: Yes.

AO: Is that the main thing of why Omega 3 fatty acids are beneficially in the
prevention?

RL: So, there’s actually several cellular mechanisms that have been proposed. Nobody
has a clear cut answer, it’s still kind of unknown, but one of the main ideas is that
CHA is in high volume in the brain, as opposed to EPA, which is in high volume
in the body, so a lot of the cardiovascular benefits of Omega 3 comes from EPA
instead of CHA. And, what we see is that CHA has actually helped in several
ways. The two main ways are in membrane fluidity. So, the membrane of the
neuron or the membrane in any cell is a lipid bilayer. So, CHA is a lipid, and
what it does is it actually bolsters this structure of the cellular membrane to
prevent or repair damage. Cellular signaling within the cells, where there are these
things called lipid rafts, has CHA, which can act as a lipid raft and transport
nutrients within the cell on this lipid raft. It helps in maintaining the cell structure,
but also in transport. The final way that DHA helps specifically in Alzheimer’s is
that it helps plaques and tangles from occurring. Plaques occur when the broken
pieces of neurons, they have a high affinity for each other, so they end up getting
tangled. So you have all these pieces like a magnet attached to each other,
creating a rubber band ball. They all stick together and create more damage. But
what DHA does is it clings and binds to these end pieces of the bits of broken
neurons and prevents them from attaching to each other, so it can prevent tangles
by insulating that. So those are kind of three mechanisms: the first 2 are general.
 Across the brain, we see it a lot in cognition and in healthy adults. But specifically
to Alzheimer’s disease, we believe the DHA can prevent these tangles by
insulating the pieces and fragments of broken cell.

AO: So I know that there isn’t a specific cure or a cause for the disease. Do you think
it is a combination of different things that causes Alzheimer’s?

RL: Yes. So we know that neurons are dying; they die at a progressive rate, and that
they’re not cleaned up properly. So when neurons normally die in their brain, we
usually see MS, Parkinson’s, or other neurodegenerative diseases. Phagocytes eat
those dead cells and clean away that debris. We don’t see this in Alzheimer’s
Disease. Instead we see these plaques building where they attach to each other,
acting like a wrecking ball, and clearing tissue that comes in their path. There are
several theories as to why some people are more prone to it than others and there
are different risk factors. One of the greatest risk factors is actually obesity.
Obesity is involved in lack of activity and poor diet, so that would be the
contributors. But obesity is also seen with increased inflammation. So there is
systemic inflammation that happens from adipose tissue that can release a lot of
free radicals and kill neurons at a fast enough rate that your phagocytes, those
macrophages and microglial cells, can’t clear them fast enough. So that’s one
theory.

There are also genetic components. APOE is a genotype where individuals are
more likely to get Alzheimer’s than others. They are MET-E4 allele carriers, so it
is very rare. Only about 4% of the population have that genotype. 1 in 5
individuals over 65 years old have Alzheimer’s Disease. So it’s more than just
genetics that’s going on. At the end of the day, we believe that it is a combination
of chronic inflammation and some component of individual genetic makeup.

AO: So I know the talk about antioxidants are controversial, but in most of the articles
that I’ve read, when it talks about the vitamins like B, E, or C, they recommend
the actual vitamin instead of a supplement. Why is it better to take the actual
vitamin rather than the supplement?

RL: Getting something from the food or consuming it endogenously is going to be

absorbed through your intestinal tract at a much higher percentage than taking it
through a multivitamin. So when you take a multivitamin or even if you take a
high level supplement, your body can only absorb so much into the bloodstream
and the rest gets passed to your kidneys. So our Kidneys are actually facilitating
 much of the breakdown of those multivitamins as opposed to an actual food,
which will slowly get broken down in the digestive tract.

In terms of omega-3 fatty acids, this is an issue that we see a lot. If you see all the
trials of omega-3’s, where people have done a control group and a supplement
group. A lot of those trial come back null, so we see that there is no difference in
supplementing with omega-3, than there is with a control group that doesn’t get
the supplement. However, we see huge effects in dietary changes. So what I
would recommend for you, because you are interested in saturated fats,
antioxidants, and omega-3’s, rather than focusing on each little piece of that
literature and breaking your thesis down into sections, I would consider it
holistically as a Mediterranean diet. This diet is a very famous nomenclature in
the research world. You can find papers specially on the diet and that
encompasses low saturated fat, high antioxidants, and high omega-3 fatty acids.
So that seems to be what you are focusing on.

AO: Yes, I think I read an article about the MIND Diet.

RL: Exactly. So what we find is when we have compare people adhering to the
Mediterranean Diet to people versus those who don’t, then we see these really
large effects. This is another reason why we think that a lot of it has to do with the
absorption from gods, as opposed to supplementation.

AO: There was this one sentence in an article that I read that confused me a little bit. It
stated “it is not clear how berry extracts can benefit plasticity and cognition, but
their effects are most likely associated with the ability to maintain metabolic
homeostasis.”

RL: So metabolic homeostasis is essentially maintaining the proper function of the cell
and of the body. So again it goes into the diabetic realm. But what you want is to
have the same amount of intake and outtake of energy. So maintaining
homeostasis means that everything is working on an even level. In terms of
plasticity, that means that the neurons are in the prime role to regenerate and
maintain their cellular structure. A lot of the ideas in chronic high inflammation
would be that the homeostatic role decreases. So you have more cell apoptosis
and in the case of diabetes, you have a high amount of insulin and poor amounts
of glucose entering the cells, along with cell starvation. Basically what you want
is metabolically for the cell to maintain this kind of natural state in order to
function at an ideal level, and we think that antioxidants help do this.
AO: I know an increase in Vitamin B is connected with a decrease in homocysteine. I
looked up what homocysteine was and I was still a little confused on exactly what
it does and why it causes an increase in the risk of Alzheimer’s, or brain
degeneration in general.

Reflection:
The interview went pretty well and I was able to get a lot of guidance as to where my
project is headed. This interview was different than my first interview as I was able to get a lot of
information from my interviewee. Dr. Regina Leckie told me many of the biological factors
involved in Alzheimer’s Disease and I was able to understand the information that was difficult
to interpret while reading articles. She also told me that saturated fats are going to be
controversial, the opposite of what my other advisor said. Dr. Leckie told me to focus my
research on omega-3 fatty acids. However, I think I will focus on both factors as they both
interest me and they both have a sufficient amount of information. In addition, she gave me some
new websites to look at and interviews to watch.
For my next interview, I plan to write more questions and subtopics on omega-3 fatty
acids and antioxidants to go further in-depth on the topic and be able to explain why these certain
health factors and nutrients cause or prevent Alzheimer’s Disease. While I was listening to my
interview, I also noticed that I tended to say “um” or “like” a lot as it was only my second time
speaking and interviewing a professional, and I was nervous. In my next interview, I will speak
slower and collect my thoughts before I speak so I sound more confident.
Before starting the interview, I was afraid that because it was over the phone and she was
driving, I would not be able to understand her clearly, but luckily, I was easily able to understand
what she was saying and the recording picked up both of our voices. At some parts of the
interview, she would go under a tunnel and the service would cut off a little bit, cutting off her
sentences. Another thing that was difficult was concentrating on the ideas she was saying
because I was nervous and kept thinking about what I would say next. Finally, another difficulty
during the interview was thinking about new ideas when we shifted to a different topic.