[Rhonda]: I think I also read one in your
papers where you did this metabolic profiling
there was a very prominent zinc deficiency
in that.
[Dale]: Yes, so for reasons that we don't
entirely understand yet, many of the people
with the type 3, the toxic sub-type have low
serum zinc, high copper-zinc ratios, and low
triglycerides.
The low triglycerides may turn out to be related
to malabsorption, we don't know for sure yet,
but we don't really understand why the people
often have these low copper-zinc ratios.
[Rhonda]: What does that mean, the copper-zinc
ratio, what is that?
[Dale]: The high copper-zinc ratio, low zinc.
[Rhonda]: Low zinc, yeah.
[Dale]: Yeah, so as, you know, copper and
zinc actually are competitive, for example,
in their absorption.
And so, too much of one actually is often
associated with too little of another.
And then typically in our society, as you
know, most of us are deficient in zinc.
There are actually about a billion people
on Earth is the estimate for zinc deficiency.
It's a very common problem because if you
have poor gastric acidity, which is common
as we age, if you're taking PPIs for GERD,
if you're taking something for reflux, you
won't absorb the zinc very well, if you have
copper piping which most of us do, the copper
will often compete with the zinc.
And so many people have a little too much
copper and a little bit too little zinc.
And in fact, it was noted over 30 years ago
that people with high copper-zinc ratios tended
to have dementia more than those with normal
copper-zinc ratios.
[Rhonda]: Wow.
So does this have something to do with it?
I know there's like over 300 to 500 different
enzymes in the body that require zinc.
So does copper then bind to those enzymes
and then sort of mess up the function or is
that like the theory?
[Dale]: So, no.
The theory is that, as you know, copper is
a generator of free radicals.
You know, copper can act like iron in that
sense.
It has a free electron in the D orbital which
does not occur with zinc.
So in general, as you indicated, in these
various enzymes, and it's hundreds, just as
you said, it is an important structural component
and it has a very specific architecture with
the enzymes that it serves, so it is a structural
thing in general.
And copper, to my knowledge, doesn't actually
replace that.
But for example, zinc is important in many
things that are related to cognitive decline,
it's important in diabetes, it's important
in functioning of insulin, it's important,
of course, in the trophic activity of insulin
and, you know, on and on.
It's important in immune responses.
So, it actually has many effects that are
related to cognition.
[Rhonda]: So it may even just be a biomarker
for something underlying going on right in
the toxic insult type of Alzheimer's disease
you're talking about.
[Dale]: It something to keep in mind when
you see that, and especially if the person
presents, and these people tend to be very
distinctive, the people who have type 3.
So, they tend to be young, and we see them
in their late 40s, mid 50s very commonly.
We've seen them as late as starting their
first symptoms in the mid-60s, but typically,
their first symptoms are currying in the 40s
and 50s.
They are often women, they are often ApoE4
negative although not always.
There are certainly people who are ApoE4 positive
to have this.
As you mentioned, they often have the low
zinc, and then they typically present in a
non-amnestic way.
Interestingly, unless they are homozygous
for E4, in which case they do present typically
with an amnestic presentation, but the ones
who are E4 negative typically present with
problems, as I mentioned earlier, executive
dysfunction problems.
And so I always ask people, are you having
trouble organizing things?
We had one person, for example, who was known
for her tremendous organizing capability and
as she started to get the problem she just
lost it.
She could not organize things that she could
do before, it's a very common complaint.
Or as I said, people will say, "Oh, I can't
calculate a tip anymore, or I can't pay the
bills anymore," anything that is math-related
or visual perception or word finding, things
like that.
