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0:00
My name is Henrik Zetterberg.
I'm a professor
of neurochemistry
at the University of
Gothenburg, Sweden,
and also at University
College London in the UK.
I will give you an update
on fluid biomarkers
for neurodegenerative
diseases in this talk.
0:17
This is a little bit
of a busy slide.
It depicts a neuron
and some other cell
types of the brain,
and what I wanted to
show on this slide
is a selection of the biomarkers
that we can measure
in biofluids now
that represent different
compartments of the neuron
and other cell
types in the brain.
To the right, you see
synaptic markers,
like SNAP-25, synaptotagmin-1
(SYT1), and NSP2a.
Then you have tau
as an axonal marker
and neurofilament light (NfL)
as another axonal marker.
A common difference
between tau and NfL
is that NfL is richer in large
caliber myelinated axons.
Whereas, tau is mostly expressed
in thin, unmyelinated axons.
To the left, you see
the neuronal soma,
at the neuronal body,
that is rich in
different proteins
like neuron-specific
enolase (NSE),
spectrin breakdown products
(SBDPs) and UCHL1.
You also see phosphorylated
tau depicted.
Phosphorylated-tau is
regarded as a marker
of tangle pathology and
that's the traditional view.
But my view on phospho-tau
is that it is more
of a direct marker of
tau phosphorylation,
which then results
in tangle pathology.
To the very left, is the
dendritic tree of the neuron
which is rich in
neurogranin, which is also
a biomarker we can
measure in biofluids.
Astrocytes and microglia,
the astroglial cells,
are rich in in S100B, GFAp,
and they also secrete
some interleukins
and other proteins that often
are inflammation-related.
Other important biomarkers
are the biomarkers
for blood-brain
barrier dysfunctions,
CSF/serum albumin
ratio and CSF PDGFRβ.
To the lower right, you
also see amyloid plaques
with Aβ proteins that
mark this pathology,
have been measured in
cerebrospinal fluid
and, as you will
hear, also in blood.
We're still missing valid
biomarkers for TDP-43 pathology,
a common pathology in
amyotrophic lateral sclerosis
and frontotemporal dementia.
A lot of research work
is ongoing to develop
better biomarkers for
TDP-43 pathology,
but we're not there yet.
α-synuclein, which is a typical
inclusion of Parkinson's disease
and other synucleinopathies,
we still do not have a
quantitative measure of
α-synuclein pathology
in biofluids.
But there is a technology
called RT-QuiC,
with which one can take
a lumbar CSF sample,
from a patient, spike in
the recombinant α-synuclein
and monitor seeded
aggregation of α-synuclein.
The seeded aggregate
is then initiated
by factors that are in
the patient sample.
That's a very interesting
concept to detect
α-synuclein pathology
qualitatively.
Now, I will continue to go
in-depth into some of these
markers that are close to
clinical implementation
and also use in clinical trials.
