TDP-43 plasma levels are higher in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Biochemistry
• Genetics

Background:

• TDP-43 is a key protein implicated in amyotrophic lateral sclerosis (ALS).
• TDP-43 forms inclusions in ALS brains, and mutations in the TARDBP gene are linked to ALS.
• While elevated in cerebrospinal fluid, TDP-43 plasma levels in ALS patients remain uninvestigated.

Purpose of the Study:

• To determine if TDP-43 plasma levels are altered in patients with amyotrophic lateral sclerosis (ALS).
• To explore the potential of TDP-43 plasma levels as a diagnostic biomarker for ALS.

Main Methods:

• Quantified TDP-43 plasma levels using sandwich ELISA in 219 ALS patients and 100 controls.
• Sequenced exon 6 of the TARDBP gene in ALS patients.
• Conducted longitudinal plasma TDP-43 measurements in a subset of ALS patients.

Main Results:

• TDP-43 plasma levels were significantly higher in ALS patients compared to controls (p=0.023).
• A positive correlation between TDP-43 plasma levels and age was observed in both patients and controls.
• Longitudinal analysis revealed stable TDP-43 levels in most patients, with a notable increase in only one individual.
• Three TARDBP variations were identified in 1.7% of the ALS cohort, but their association with TDP-43 plasma levels was unclear.

Conclusions:

• Elevated TDP-43 plasma levels show potential as a diagnostic biomarker for amyotrophic lateral sclerosis (ALS).
• The study did not establish a clear genotype-phenotype relationship between TARDBP variations and TDP-43 plasma levels in this cohort.