| Title: | Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis : New Insights From Biomarker Studies |
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| Author: | Reyes-Leiva, David; Dols Icardo, Oriol; Sirisi, Sonia; Cortés-Vicente, Elena; Turon-Sans, Janina; de Luna Salva, Noemí; Blesa, Rafael; Belbin, Olivia; Montal, Victor; Alcolea, Daniel; Fortea, Juan; Lleó, Alberto; Rojas-Garcia, Ricard; Illán-Gala, Ignacio; Universitat Autònoma de Barcelona |
| Abstract: | Altres ajuts:Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00408 to AL), Fundació La Marató de TV3 (044412 to RB and 201437.10 to RR-G). |
| Abstract: | Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) lie at opposing ends of a clinical, genetic, and neuropathological continuum. In the last decade, it has become clear that cognitive and behavioral changes in patients with ALS are more frequent than previously recognized. Significantly, these non-motor features can impact the diagnosis, prognosis, and management of ALS. Partially overlapping neuropathological staging systems have been proposed to describe the distribution of TAR DNA-binding protein 43 (TDP-43) aggregates outside the corticospinal tract. However, the relationship between TDP-43 inclusions and neurodegeneration is not absolute and other pathophysiological processes, such as neuroinflammation (with a prominent role of microglia), cortical hyperexcitability, and synaptic dysfunction also play a central role in ALS pathophysiology. In the last decade, imaging and biofluid biomarker studies have revealed important insights into the pathophysiological underpinnings of extra-motor neurodegeneration in the ALS-FTLD continuum. In this review, we first summarize the clinical and pathophysiological correlates of extra-motor neurodegeneration in ALS. Next, we discuss the diagnostic and prognostic value of biomarkers in ALS and their potential to characterize extra-motor neurodegeneration. Finally, we debate about how biomarkers could improve the diagnosis and classification of ALS. Emerging imaging biomarkers of extra-motor neurodegeneration that enable the monitoring of disease progression are particularly promising. In addition, a growing arsenal of biofluid biomarkers linked to neurodegeneration and neuroinflammation are improving the diagnostic accuracy and identification of patients with a faster progression rate. The development and validation of biomarkers that detect the pathological aggregates of TDP-43 in vivo are notably expected to further elucidate the pathophysiological underpinnings of extra-motor neurodegeneration in ALS. Novel biomarkers tracking the different aspects of ALS pathophysiology are paving the way to precision medicine approaches in the ALS-FTLD continuum. These are essential steps to improve the diagnosis and staging of ALS and the design of clinical trials testing novel disease-modifying treatments. |
| Subject(s): | -Amyotrophic lateral sclerosis (ALS) -Neuroimage -Cerebrospinal fluid (CSF) -Biomarker (BM) -Neuropathology -TDP-43 = TAR DNA-binding protein 43 -Frontotemporal lobar degeneration -Frontotemporal dementia (FTD) |
| Rights: | open access
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| Document type: | Article de revisió |
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| Uri: | https://ddd.uab.cat/record/252268 |
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