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- General Strategies in Biomarker Research
-
1. The proteomic revolution
- Dr. Larry Gold
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2. Lipid biomarkers: lipidomics of the macrophage and plasma lipidomes
- Prof. Edward A. Dennis
- New Tools for Biomarker Research
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5. Development of glyco-biomarkers using glycoproteomics technologies
- Dr. Hisashi Narimatsu
-
6. Circulating nucleic acids as biomarkers in cancer patients
- Prof. Klaus Pantel
- Specific Disease Applications
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7. Biomarkers in breast cancer
- Prof. Joe Duffy
-
8. Bacterial biomarkers
- Dr. Christiane Honisch
-
9. Diabetes biomarkers
- Prof. Naveed Sattar
-
10. Gene networks, brain networks: understanding schizophrenia
- Dr. Daniel Weinberger
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11. Biomarkers for Huntington's disease - promises and challenges
- Prof. Sarah Tabrizi
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12. Update on fluid biomarkers for neurodegenerative diseases
- Prof. Henrik Zetterberg
-
13. Biomarkers in osteoarthritis
- Dr. Ali Mobasheri
- Biomarkers in Drug Discovery and Delivery
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14. Pharmacogenomics: emphasis on clinical drug development
- Dr. Amelia Warner
-
15. Biomarkers in drug development: potential use and challenges
- Dr. Abdel-Bassett Halim
- Biomarkers in development, nutrition, and health
-
18. Ethnic differences in nutrition
- Prof. Jose Ordovas
-
19. Non-invasive prenatal diagnostics
- Prof. Y. M. Dennis Lo
-
20. Epigenetic biomarkers in cancer
- Prof. Bob Brown
- Archived Lectures *These may not cover the latest advances in the field
-
21. Biomarkers for Alzheimer's disease
- Prof. Henrik Zetterberg
Printable Handouts
Navigable Slide Index
- Introduction
- Fluid biomarkers and neurodegenerative disease
- A = amyloid pathology
- CSF Aβ42 is decreased in Alzheimer’s disease
- CSF Aβ42 is a marker of amyloid plaque pathology
- CSF Aβ42 concentration correlates with amyloid PET
- CSF Aβ42 concentration may be decreased in neuroinflammatory conditions
- CSF Aβ42 concentration may be decreased in normal pressure hydrocephalus
- Constitutively low Aβ producers who are close to the Aβ42 cutpoint for positivity
- CSF Aβ42/40 (or Aβ38) and PET Aβ
- The CSF Aβ42/Aβ40 ratio in clinical practice
- CSF Aβ42/Aβ40 ratio: longitudinal data (1)
- CSF Aβ42/Aβ40 ratio: longitudinal data (2)
- How about plasma Aβ?
- Sensitive and precise mass spec methods work
- Plasma Aβ in the Insight46 cohort
- The challenge
- Fluid biomarkers for amyloid pathology: conclusions
- T = tau pathology
- CSF P-tau is increased in AD
- CSF P-tau increases only in AD
- Differential detection of AD measuring different phospho-forms of tau in CSF
- Different forms of P-tau can be measured in plasma
- Donanemab lowers plasma P-tau217
- Aducanumab lowers plasma P-tau181
- Fluid biomarkers for tau pathology: conclusions
- N = neurodegeneration
- CSF neurofilament light (NfL)
- CSF NfL: predictor of disease progression in MCI
- CSF NfL in relation to brain structure
- CSF NfL dynamics: normalization in response to successful treatment
- CSF NfL dynamics in spinal muscular atrophy
- CSF NfL dynamics in Huntington’s disease
- Plasma NfL correlates with CSF NfL
- Plasma NfL dynamics in Huntington’s disease
- Plasma NfL dynamics in Alzheimer’s disease (1)
- Plasma NfL dynamics in Alzheimer’s disease (2)
- Fluid biomarkers for neurodegeneration: conclusions
- The Alzbiomarker database 2021 is now live!
- Thank you!
Topics Covered
- Fluid biomarker candidates for neurodegenerative disease
- Amyloid pathology
- CSF and plasma/serum NfL
- CSF Aβ42 in Alzheimer’s disease and neuroinflammatory diseases
- Tau pathology in Alzheimer’s disease
- Neurodegeneration
- CSF and plasma NfL as biomarkers for disease progression
- Drug treatment and NfL levels
Links
Series:
- Biomarkers
- Drug Discovery and Development in the Neurosciences
- The Genetic Basis of Neurological Disorders
Categories:
Therapeutic Areas:
External Links
Talk Citation
Zetterberg, H. (2022, August 31). Update on fluid biomarkers for neurodegenerative diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 31, 2024, from https://doi.org/10.69645/SGST9313.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Henrik Zetterberg has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Methods
Transcript
Please wait while the transcript is being prepared...
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.