Good Essay Collection Blood biomarkers in neurology

Special Issue on Blood Biomarkers In Neurology

Issue Edited by: Henrik Zetterberg, Johan Zelano

REVIEW ARTICLES

Blood biomarkers of peripheral neuropathy

Blood biomarkers of peripheral neuropathy

Alexander M.
Rossor, Mary M.
Reilly

The notion that blood tests could be used to diagnose and monitor peripheral nerve damage has always seemed fanciful, however, with the development of ultrasensitive protein assays, their detection limits are lower than traditional ELISA techniques, allowing markers of nerve damage such as NFL to be accurately measured
in the blood.
However, a key obstacle is the inability to distinguish between central and peripheral nerve degeneration
.
Nevertheless, these protein biomarkers appear to be effective in identifying patients with peripheral neuropathy compared to controls and have shown effectiveness
as markers of disease activity in patients with rapidly progressing peripheral neuropathy such as vasculitis and amyloidosis.
The use of axonal protein biomarkers such as NFL in slowly progressive diseases without significant axon loss (e.
g.
, CMT, CIDP, and multifocal motor neuropathy) is uncertain
.
Measurements of correlated circulating microRNAs show great promise because quantification techniques are well established to select specific microRNAs
specific to disease processes.

Article Links:

https://onlinelibrary.
wiley.
com/doi/10.
1111/ane.
13650

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Blood based biomarkers for movement disorders

Blood biomarkers of dyskinesia

Huw R.
Morris

The development of blood biomarkers for AD, as well as the identification of NfL as a prognostic marker and diagnostic marker for atypical Parkinson's disease, may have a direct impact on patient selection and stratification of clinical trials, which may then be applied to clinical practice
.
More natural, long-term studies are likely needed to evaluate the additional role of blood biomarkers beyond standard clinical practice and to directly assess the clinical benefits
of early diagnosis and more accurate prognosis in everyday practice.
The gold standard for most diagnostic research remains clinical diagnosis using standard diagnostic criteria, or clinical diagnosis supplemented by PET protein imaging studies, which in my opinion represents a reasonable proof of concept using blood biomarkers, rather than a definitive proof
of benefit in a routine clinical setting.
A multimodal approach that combines blood biomarkers with demographics, genetics, imaging, and clinical features has the potential to maximize diagnostic and predictive accuracy
, in addition to being able to assess the role of biomarkers in a holistic clinical context.

In addition to AD biomarkers and NfL, the development of specific tau and α-synuclein blood biomarkers for dyskinesia has so far been disappointing, but rapid advances in protein aggregation and high-throughput multiplexing suggest that new biomarker detections, profiles, and profiles will continue to be developed, evaluated, and integrated into protocols for future clinical trials and clinical practice
.

Article Links:

https://onlinelibrary.
wiley.
com/doi/10.
1111/ane.
13700

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Blood biomarkers in epilepsy

Blood biomarkers of epilepsy

Rakesh Kumar Banote, Sarah Akel, Johan Zelano

In this review, we provide a narrative overview
of potential blood biomarkers of epilepsy.
To accelerate the use of these biomarkers in clinical practice, further research
is needed.
Advances in this area may require the collection of large well-characterized samples
from longitudinal studies of well-defined patient cohorts.
Special efforts should be made to classify
epilepsy and seizure types in more detail.
Epilepsy is a very heterogeneous disorder, and it may not be possible to identify biomarkers of epilepsy in a case or in the study of a specific seizure type
.
Working together to create common data elements for inclusion in epilepsy blood biomarker studies may increase the likelihood of
data sharing and subgroup analysis.
Candidate markers need to be compared between different patient groups (with epilepsy vs no epilepsy, recent seizures vs epileptic, etc.
).

After that, the sensitivity and specificity
of each clinical application need to be determined.
Diagnosing blood biomarkers is still a long way off, but the field is moving
forward.

Article Links:

https://onlinelibrary.
wiley.
com/doi/10.
1111/ane.
13616

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Blood biomarkers in ALS: challenges, applications and novel frontiers

Blood biomarkers in amyotrophic lateral sclerosis: challenges, applications, and new frontiers

Ellie Sturmey, Andrea Malaspina

TDP-43 proteopathy is a typical neuropathological event
in most patients with amyotrophic lateral sclerosis and some patients with FTD.
Mislocalization of TDP-43 from the nucleus to the cytoplasm leads to loss of nuclear function, affecting RNA translation of a large number of proteins, including the protein unc-13 homolog a (UNC13A).

In the case of UNC13A, this results in random inclusion of so-called cryptoexons (derived from non-conserved intron sequences) and the formation of cryptopeptides
when translated into the final protein.
UNC13A as a regulator of synaptic function and neurotransmitter release
.
In amyotrophic lateral sclerosis (ALS), cryptic exon clathrates in UNC13A, and other loss-of-function TDP-43-controlled proteins may produce abnormal and toxic proteomes
.
If there are two single nucleotide polymorphisms (SNPs), rs12973192 and rs12608932, located within or near the exome insertion site, the risk of inclusion of exons in UNC13A increases
.
In genome-wide association studies, both have been shown to increase the risk of
ALS.
For example, in sporadic ALS patients, rs12608932 SNP is associated with earlier onset in patients with ALS in Europe and the United States, and is associated with shorter survival times and frontotemporal degeneration The loss of UNC13A function leads to a decrease in miR-3911 expression, which is usually detected in neuron-derived extracellular plasma vesicles, Therefore, the detection of miR-3911 downregulation is an alternative to UNC13a-related pathology and can be detected without resorting to expensive whole genome sequencing
。

Premature merging of crypteons and formation of abnormal proteins, as indicated by other proteins downstream of UNC13A and TDP-43 loss of function, may be a decisive pathological event
in amyotrophic myelosis.
It may constitute a paradigm shift in biomarker research for this neurodegenerative disease, especially since TDP-43 pathology is largely ALS/
ftd-specific.
Therefore, cryptopeptide formation is a potential source of biomarkers for early diagnosis and stratification
of specific endophenotypes in ALS patients.
Loss of normal function and cryptoexon inclusion of UNC13A can also be used as pharmacological biomarkers for future therapeutic interventions aimed at preventing the formation
of amyotrophic lateral sclerosis cryptopeptides.
NFS undoubtedly shapes the outlook for neurodegenerative disease disease surveillance and contributes to the prognostic features of amyotrophic lateral sclerosis, and the discovery of amyotrophic lateral sclerosis cryptoproteins may provide the basis
for the next generation of biomarkers for this incurable disease.

Article Links:

https://onlinelibrary.
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com/doi/10.
1111/ane.
13698

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Fluid biomarkers in stroke: From animal models to clinical care

Liquid biomarkers of stroke: from animal models to clinical care

Alexandre Dias, Lénia Silva, João Moura, Denis Gabriel, Luis F.
Maia

Stroke is the leading cause of
death and disability worldwide.
Stroke prevention, early diagnosis and effective acute treatment are priorities
that successfully influence stroke death and disability.
Liquid biomarkers improve the differential diagnosis of stroke, stratification of patients for acute care, and individualized rehabilitation
after stroke.
In our current work, we describe the application of stroke animal models to fluid biomarker studies through a systematic review of the PubMed and Scopus databases, and then review the literature translating it into human stroke care settings and future prospects
in the field.
We found an increasing number of publications, but limited
clinical translations.
Animal studies are very heterogeneous and cannot explain the few human traits that appear in stroke, and, importantly, only a few such studies use human cohorts to validate biomarker findings
.
Clinical studies have identified attractive candidate substances, including proteins and circulating nucleic acids, that could help shape a more personalized approach to
stroke care.
Nevertheless, the complexity of brain tissue and the fact that different brain pathologies share lesion biomarkers make this task challenging due to the low
specificity of biomarkers.
In addition, study design and lack of validation cohorts may hinder the formal integration
of biomarkers in different steps of stroke diagnosis and treatment.
To overcome these issues, recent critical studies on biomarker dynamics in individual patients provide added value
for diagnosing and predicting early patient outcomes.
Currently, the most consistent protein biomarkers for stroke diagnosis and short- and long-term prognosis are associated
with tissue damage at neuronal (TAU), axon (NFL), or astroglial (GFAP and S100β) levels.
Most promising nucleic acids are microRNAs (miR) because of their stability and ease of availability
in plasma.
Still, clinical validation and standardized quantification put them one step
behind comparative proteins as stroke biomarkers.
Ultimately, the definition of clinically relevant biomarker panels and the optimization of rapid, sensitive biomarker measurements in blood, combined with clinical and neuroimaging data, will pave the way for
personalized stroke care.

Article Links:

https://onlinelibrary.
wiley.
com/doi/10.
1111/ane.
13668

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