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Open AccessArticle

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

1
UMR 1253, iBrain, University of Tours, Inserm, 37000 Tours, France
2
Centre Constitutif SLA, CHRU Bretonneau, 37000 Tours, France
3
CHU Tours, Service de Biochimie et Biologie Moléculaire, 37000 Tours, France
4
CHU Tours, Service de MNIV, 37000 Tours, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2911; https://doi.org/10.3390/ijms21082911
Received: 4 March 2020 / Revised: 15 April 2020 / Accepted: 16 April 2020 / Published: 21 April 2020
(This article belongs to the Special Issue Peripheral Biomarkers in Neurodegenerative Diseases 2.0)
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sensitive molecules may be of interest in clinical practice. For example, markers related to other neurodegenerative diseases such as Alzheimer’s disease (AD) could be fully explored. Here, we compared baseline levels of amyloidβ1-42 (Aβ1-42), total Tau, and phosphorylated-Tau (phospho-Tau) protein in the cerebrospinal fluid (CSF) of ALS patients to controls and correlated it with clinical parameters of ALS progression collected over 12 months. We observed increased levels of Aβ1-42 (controls: 992.9 ± 358.3 ng/L; ALS: 1277.0 ± 296.6 ng/L; p < 0.0001) and increased Aβ1-42/phospho-Tau ratio and Innotest Amyloid Tau Index (IATI) (both p < 0.0001). IATI and the phospho-Tau/total Tau ratio correlated positively with ALSFRS-R and weight at baseline. Multivariate analysis revealed that baseline ALSFRS-R was associated with Aβ1-42 and phospho-Tau/total Tau ratio (p = 0.0109 and p = 0.0013, respectively). Total Tau and phospho-Tau levels correlated negatively with ALSFRS-R variation at months 6 and 9, respectively (p = 0.02 and p = 0.04, respectively). Phospho-Tau/total Tau ratio correlated positively with ALSFRS-R variation at month 9 (p = 0.04). CSF levels of Aβ1-42 could be used as a complementary tool to ALS diagnosis, and total Tau and phospho-Tau levels may help establishing the prognosis of ALS. Further studies merit exploring the pathophysiological mechanisms associated with these markers. Despite their lack of specificity, phospho-Tau/total Tau and Aβ1-42 should be combined to other biological and clinical markers in order to improve ALS management. View Full-Text
Keywords: ALS; biomarker; Aβ1-42; total Tau; CSF ALS; biomarker; Aβ1-42; total Tau; CSF
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Lanznaster, D.; Hergesheimer, R.C.; Bakkouche, S.E.; Beltran, S.; Vourc’h, P.; Andres, C.R.; Dufour-Rainfray, D.; Corcia, P.; Blasco, H. Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci. 2020, 21, 2911.

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