Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis: New Insights From Biomarker Studies
Por:
Reyes-Leiva, D, Dols-Icardo, O, Sirisi, S, Cortes-Vicente, E, Turon-Sans, J, De Luna, N, Blesa, R, Belbin, O, Montal, V, Alcolea, D, Fortea, J, Lleo, A, Rojas-Garcia, R, Illan-Gala, I
Publicada:
18 ene 2022
Resumen:
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.
Filiaciones:
Reyes-Leiva, D:
Univ Autonoma Barcelona, Neuromusc Dis Unit, Dept Neurol, Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain
Dols-Icardo, O:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Sirisi, S:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Cortes-Vicente, E:
Univ Autonoma Barcelona, Neuromusc Dis Unit, Dept Neurol, Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain
Turon-Sans, J:
Univ Autonoma Barcelona, Neuromusc Dis Unit, Dept Neurol, Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain
De Luna, N:
Univ Autonoma Barcelona, Neuromusc Dis Unit, Dept Neurol, Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain
Blesa, R:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Belbin, O:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Montal, V:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
Rojas-Garcia, R:
Univ Autonoma Barcelona, Neuromusc Dis Unit, Dept Neurol, Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERER, Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain
Illan-Gala, I:
Univ Autonoma Barcelona, Sant Pau Memory Unit, Dept Neurol, Biomed Res Inst Sant Pau,Hosp Santa Creu Sant Pau, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurode, Madrid, Spain
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