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Depression and Heart Disease

Biomarkers and Alzheimer’s Disease: Dr. Neil Buckholtz

– We know a lot more
about Alzheimer’s disease today than we knew ten years ago, and one of the reasons is
because we now have biomarkers that can tell us
about the processes going on in the living human brain. So, we can look
at what’s going on in beta amyloid
in the human brain, what’s going on
in various aspects of changes
in the brain structure. It’s not to say that we still
don’t need animal studies. We still need
post-mortem studies. But, this has been a major
change over the past ten years. Biomarkers are measurements that indicate
biological processes, both normal and abnormal,
in the brain, as well as
pathological processes, and responses to interventions
such as drugs. The kinds of biomarkers
that we look at in Alzheimer’s disease
are basically two kinds. One is a measurement
of the structure of the brain, and that’s done with
magnetic resonance imaging. And so we can see changes in the structure of the brain
over time as Alzheimer’s disease
progresses. The other major
kind of biomarker is a functional biomarker and this uses
Positron Emission Tomography to look at the function
of the brain. And there are
two kinds of PET or Positron Emission
Tomography studies that are being done right now. One is to look at brain energy
metabolism with glucose and the other is to look
at beta amyloid in the living human brain. We hope that there will be
other kinds of PET measurements, such as tau,
coming up very shortly. The Alzheimer’s Disease
Neuroimaging Initiative or ADNI has played a huge role
in the development and use of biomarkers
for Alzheimer’s disease. It was set up in 2004
as a longitudinal study to look at changes
in a number of biomarkers over time in people who were
cognitively normal but aged, in people with
mild cognitive impairment, and in people
with Alzheimer’s disease. It has looked at
both structural imaging using magnetic resonance imaging and functional imaging
using various kinds of PET to look at both brain energy
metabolism with glucose, and also beta amyloid. ADNI has provided a database that’s accessible to anyone
anywhere in the world. So, this is a public database
that’s had a huge effect on our ability to understand
Alzheimer’s disease. Through the use of
various kinds of biomarkers, both neuroimaging biomarkers as well as biomarkers
in cerebrospinal fluid, we now believe
that beta amyloid comes in very early
in the disease process, and then basically
plateaus later on. Another biomarker, tau,
comes in a little later, and is actually changed
by beta amyloid. Beta amyloid seems to increase
the amount of tau that we see. So, by the use of these
various kinds of biomarkers, we can get a staging
of the disease process from early beta amyloid changes
to tau changes, to functional changes,
looking at glucose metabolism and then later on to other
kinds of functional changes with various kinds of
measurements of memory. So, we now have
a better understanding of disease progression, from the very earliest
pre-symptomatic stages through mild
cognitive impairment and into Alzheimer’s disease. Biomarkers will be
very important in helping us to determine
the effectiveness of treatments. Many of the drugs
that are in development now focus on various aspects
of beta amyloid metabolism. So, from our ability to look
at beta amyloid metabolism in the living brain, using PET,
and also looking at cerebrospinal fluid measurements
of beta amyloid, we will be able to determine whether these drugs
are having the effect that we think that they’re
having in the brain. There are biomarkers
in development that, hopefully,
will provide information about other mechanisms
in the brain that are also important
in Alzheimer’s disease. One of these clearly is tau. However, we haven’t had a good neuroimaging
measure of tau up until very recently. There are now a number of
studies that are being done which hopefully will provide
the kinds of information that we need
to be able to use these various kinds of
imaging modalities to visualize tau
in the living human brain. Right now, these biomarkers
are not ready for clinical use
in the community. They’re still for research. But, we’re hoping
that either through various kinds of
imaging modalities, through cerebrospinal
fluid measures, or what we would really like
is a measurement in the blood that can be used for early diagnosis
or disease progression.

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