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Keywords: Amyotrophic lateral sclerosis, Biomarkers, Cerebrospinal fluid, Cryptic peptide, Frontotemporal dementia, Hepatoma derived growth factor 2, Neurodegeneration, TAR DNA-binding protein 43

This letter demonstrates the potential of novel cryptic proteins resulting from TAR DNA-binding protein 43 (TDP-43) dysfunction as markers of TDP-43 pathology in neurodegenerative diseases.This letter demonstrates the potential of novel cryptic proteins resulting from TAR DNA-binding protein 43 (TDP-43) dysfunction as markers of TDP-43 pathology in neurodegenerative diseases.

In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus. TDP-43 loss leads to cryptic exon inclusion but a role in other RNA processing events remains unresolved. Here, we show that loss of TDP-43 causes widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., and ) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.

Bioelectrical impedance analysis (BIA) is a noninvasive method recently introduced for body fluid evaluation in healthy subjects. The purpose of this paper is to verify the reliability of bioelectrical measurements in extracellular water (ECW) prediction in healthy subjects and in fluid retention states. We studied 40 subjects (19 males and 21 females) aged 21-81 years; 22 were healthy subjects, 12 were affected by chronic heart failure, and 6 by chronic renal failure. In all subjects resistance (R) and reactance (Xc) at 1 and 50 kHz corrected for height were compared with ECW measured by the bromide dilution method. Our results suggested a different behavior of the current in fluid-retention states with respect to healthy subjects. ECW was best predicted by resistance at 1 kHz corrected for height, group (considered as dummy variable), weight and gender (R² = 0.89, p < 0.001, SEE = 1.7 liters). The bioelectrical impedance analysis at 50 kHz explained the 89% of ECW variability when resistance and reactance corrected for height are considered with gender group and weight (R² = 0.89, p < 0.001, SEE = 1.7 liters). In conclusion, the bioelectrical method at 1 kHz can be considered sufficiently accurate in ECW prediction in healthy subjects and in fluid retention states. Also, the bioelectrical impedance analysis at 50 kHz is useful for predicting ECW, but his role must be further investigated.