Περίληψη:
Objective To assess neurofilaments as neurodegenerative biomarkers in
serum of patients with Friedreich's ataxia. Methods Single molecule
array measurements of neurofilament light (NfL) and heavy chain (pNfH)
in 99 patients with genetically confirmed Friedreich's ataxia.
Correlation of NfL/pNfH serum levels with disease severity, disease
duration, age, age at onset, and GAA repeat length. Results Median serum
levels of NfL were 21.2 pg/ml (range 3.6-49.3) in controls and 26.1
pg/ml (0-78.1) in Friedreich's ataxia (p = 0.002). pNfH levels were 23.5
pg/ml (13.3-43.3) in controls and 92 pg/ml (3.1-303) in Friedreich's
ataxia (p = 0.0004). NfL levels were significantly increased in younger
patients (age 16-31 years, p < 0.001) and patients aged 32-47 years (p =
0.008), but not in patients of age 48 years and older (p = 0.41). In a
longitudinal assessment, there was no difference in NfL levels in 14
patients with repeated sampling 2 years after baseline measurement.
Levels of NfL correlated inversely with GAA1 repeat length (r = - 0.24,
p = 0.02) but not with disease severity (r = - 0.13, p = 0.22), disease
duration (r = - 0.06, p = 0.53), or age at onset (r = 0.05, p = 0.62).
Conclusion Serum levels of NfL and pNfH are elevated in Friedreich's
ataxia, but differences to healthy controls decrease with increasing
age. Long-term longitudinal data are required to explore whether this
reflects a selection bias from early death of more severely affected
individuals or a slowing down of the neurodegenerative process with age.
In a pilot study over 2 years of follow-up-a period relevant for
biomarkers indicating treatment effects-we found NfL levels to be
stable.
Συγγραφείς:
Hayer, Stefanie Nicole
Liepelt, Inga
Barro, Christian
Wilke,
Carlo
Kuhle, Jens
Martus, Peter
Schoels, Ludger
Schulz,
Joerg Bernhard
Reetz, Kathrin
Fedosov, Kathrin
Didszun,
Claire
Klockgether, Thomas
Giordano, Ilaria
Pandolfo,
Massimo
Depondt, Chantal
Rai, Myriam
Boesch, Sylvia and
Nachbauer, Wolfgang
Eigentler, Andreas
Indelicato, Elisabetta
and Giunti, Paola
Parkinson, Michael
Manso, Katarina and
Thomas-Black, Gilbert
Garcia-Moreno, Hector
Solanky, Nita and
Abeti, Rosella
Polke, James
Labrum, Robin
Garrido, Rodriguez
de Rivera Francisco Javier
Mascias, Javier
Velasco, Sanchez Sara
and Garcia, Secades Sergio
Mariotti, Caterina
Nanetti, Lorenzo
and Castaldo, Anna
Mongelli, Alessia
Fichera, Mario and
Klopstock, Thomas
Karin, Ivan
Stendel, Claudia
Radelfahr,
Florentine
Durr, Alexandra
Biet, Marie
Charles, Perrine and
Ewenczyk, Claire
Just, Jennifer
Koutsis, Georgios
Walsh,
Richard
Bertini, Enrico
EFACTS Study Grp
