Professor
Claude Wischik is board certified in
psychiatry and Professor of Old Age
Psychiatry at the University of
Aberdeen, Scotland. A pioneer in tau
research, Prof. Wischik’s work on
tau pathology began in 1985 in the
laboratory of Sir Martin Roth, who
was the first to correlate tangles
with Alzheimer’s dementia, and later
he worked with Sir Aaron Klug (Nobel
Laureate) at Cambridge University.
Gary Barg: Dr.
Wischik, what is the current state
of the science of determining the
cause and possible treatment for
Alzheimer’s disease?
Claude Wischik:
For the last twenty years or so the
field has focused almost exclusively
on the amyloid hypothesis. (Ed.
note: The amyloid theory describes
how an increase in secreted
beta-amyloid peptides leads to the
formation of plaques eventually
resulting in the death of brain
cells.) I think that view has been
severely dented by repeated trial
failures.
The main alternative is the
theory that we’ve backed since the
mid-80s. And that is the tau theory.
This builds on Dr.Alzheimer’s
original discovery. Dr. Alzheimer
discovered a lesion in the brain
called the tangle, which are
abnormal fibers forming inside nerve
cells. These nerve cells are the
ones critical for all communication
from one part of the brain to the
other. We found that the amount of
aggregated tau protein going into
these tangles is really driving how
demented people are.
Gary Barg: Is
there a single target potentially
identifiable for treatment of the
disease? Or is it inherently more
complicated?
Claude Wischik:
I think tau plays an important role,
but probably tau is also not the
whole story. It’s just that tau is a
better story than the amyloid. If I
can put it in simple terms: as nerve
cells age, their garbage disposal
machinery becomes less and less
efficient at handling bits of junk
that form during the normal wear and
tear of the cells. Once that process
is initiated, it acts as a seed on
which the tau aggregation can begin.
And once tau aggregation begins, it
just goes on and on, sucking more
and more of the normal tau protein
into these toxic aggregates.
And what’s worse is that this
process spreads from one nerve cell
to the next. I do sincerely believe
that a tau based treatment will
provide a way forward in the near
term. Not just that, it may well be
the only story that’s going to break
in the next seven years for a
potential successful treatment.
Gary Barg: Can
you discuss the value of considering
clinical trials for Alzheimer’s
caregivers?
Claude Wischik:
Caregivers have to weigh a very
simple odds calculation. They’ve got
to do this risk analysis. One, it’s
a dead certainty that if I have the
disease, it’s going to progress and
at some point, I’m going to end up,
or the person I care for is going to
end up, in a nursing home. On the
other hand, you have the
possibility, but by no means the
certainty, that a certain
experimental treatment will delay or
stop or protect from that outcome.
It’s a very simple risk calculation
to say you’re much better off trying
an approach that may give hope
versus the dead certainty of just
staying where you are.
So for the caregiver and the
patient, it’s in their own selfish
best interests that they participate
in clinical trials. Then there’s the
more altruistic thing which is that
their participation in the trials
will hasten the day when treatments
can actually help. From a patient
caregiver point of view, the odds
are very simple—certainty versus the
possibility of a way out.
