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- 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.