Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

Agnello, Luisa; Colletti, Tiziana; Sasso, Bruna Lo; Vidali, Matteo; Spataro, Rossella; Gambino, Caterina Maria; Giglio, Rosaria Vincenza; Piccoli, Tommaso; Bivona, Giulia; Bella, La; Ciaccio, Marcello

doi:10.1111/ene.14789

Cited by 27 publications

(25 citation statements)

References 38 publications

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“…The sensitivity and specificity of this ratio were equal to 80% and 77%, respectively (see Table 1). 73 In CSF, a number of chitinase and chitinase‐like proteins have been shown to be significantly elevated in ALS patients compared to mimics, including chitotriosidase (CHIT1), chitinase‐3‐like protein 1 (YKL‐40; or CHI3L1), and chitinase‐3‐like protein 2 (YKL‐39; or CHI3L2) (see Table 1). 74,75 In serum, a significant difference was not reported when the same analyses were conducted 74,75 .…”

Section: Utilisation Of Blood Biomarkers In Alsmentioning

confidence: 99%

Blood biomarkers in ALS : challenges, applications and novel frontiers

Sturmey

Malaspina

2022

Acta Neuro Scandinavica

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Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease among adults. With diagnosis reached relatively late into the disease process, extensive motor cell loss narrows the window for therapeutic opportunities. Clinical heterogeneity in ALS and the lack of disease‐specific biomarkers have so far led to large‐sized clinical trials with long follow‐up needed to define clinical outcomes. In advanced ALS patients, there is presently limited scope to use imaging or invasive cerebrospinal fluid (CSF) collection as a source of disease biomarkers. The development of more patient‐friendly and accessible blood biomarker assays is hampered by analytical hurdles like the matrix effect of blood components. However, blood also provides the opportunity to identify disease‐specific adaptive changes of the stoichiometry and conformation of target proteins and the endogenous immunological response to low‐abundance brain peptides, such as neurofilaments (Nf). Among those biomarkers under investigation in ALS, the change in concentration before or after diagnosis of Nf has been shown to aid prognostication and to allow the a priori stratification of ALS patients into smaller sized and clinically more homogeneous cohorts, supporting more affordable clinical trials. Here, we discuss the technical hurdles affecting reproducible and sensitive biomarker measurement in blood. We also summarize the state of the art of non‐CSF biomarkers in the study of prognosis, disease progression, and treatment response. We will then address the potential as disease‐specific biomarkers of the newly discovered cryptic peptides which are formed down‐stream of TDP‐43 loss of function, the hallmark of ALS pathobiology.

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Section: Utilisation Of Blood Biomarkers In Alsmentioning

confidence: 99%

Blood biomarkers in ALS : challenges, applications and novel frontiers

Sturmey

Malaspina

2022

Acta Neuro Scandinavica

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“…Their early identification is crucial, but still today, it is challenging. CSF biomarkers represent precious tools for assessing neurodegenerative disorders providing in vivo information on the underlying pathology [ 21 , 22 , 23 , 24 ]. Specifically, CSF is an ideal biofluid due to its proximity to the brain parenchyma, the moderately low cost in comparison to positron emission tomography imaging, and the safety of lumbar puncture.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

Agnello

Sasso

Vidali

et al. 2022

JCM

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(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) α-syn levels in several neurological disorders; (2) Methods: We measured CSF α-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer’s Disease (AD), cerebrovascular diseases, inflammatory central nervous system diseases, other neurological diseases, Parkinson’s Disease (PD), and peripheral neuropathy; (3) Results: Patients with PD showed the lowest and patients with AD the highest levels of CSF α-syn (1372 vs. 2912 pg/mL, respectively, p < 0.001). In AD patients, α-syn levels were significantly associated with tau proteins; (4) Conclusions: α-syn could represent a biomarker of neurodegenerative diseases.

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“…Neurodegenerative diseases are an important health burden and their early identification is crucial, but this is still challenging today. CSF biomarkers represent precious tools for assessing neurodegenerative disorders, providing in vivo information on the underlying pathology [ 23 , 24 , 25 , 26 , 27 ]. Specifically, CSF is an ideal biofluid due to its proximity to the brain parenchyma, the lower intrinsic protease activity than blood, the moderately low cost in comparison to positron emission tomography (PET) imaging and the safety of lumbar puncture.…”

Section: Discussionmentioning

confidence: 99%

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

et al. 2021

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(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.

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Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

Cited by 27 publications

References 38 publications

Blood biomarkers in ALS : challenges, applications and novel frontiers

Blood biomarkers in ALS : challenges, applications and novel frontiers

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

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