Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis: New Insights From Biomarker Studies.
TDP-43 = TAR DNA-binding protein 43
amyotrophic lateral sclerosis (ALS)
biomarker (BM)
cerebrospinal fluid (CSF)
frontotemporal dementia (FTD)
frontotemporal lobar degeneration
neuroimage
neuropathology
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2021
2021
Historique:
received:
30
07
2021
accepted:
09
12
2021
entrez:
4
2
2022
pubmed:
5
2
2022
medline:
5
2
2022
Statut:
epublish
Résumé
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
Identifiants
pubmed: 35115992
doi: 10.3389/fneur.2021.750543
pmc: PMC8804092
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
750543Informations de copyright
Copyright © 2022 Reyes-Leiva, Dols-Icardo, Sirisi, Cortés-Vicente, Turon-Sans, de Luna, Blesa, Belbin, Montal, Alcolea, Fortea, Lleó, Rojas-García and Illán-Gala.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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