A new study has found that an RNA-binding protein called TDP-43 could be a promising new biomarker for diagnosing amyotropic lateral sclerosis
“Our systematic review and meta-analysis reveals early supportive data indicating that TDP-43 detected in the CSF of patients with FTD-ALS spectrum disorders in particular ALS patients could be a promising biomarker in these diseases,” wrote senior author Suvankar Pal, MD, of the University of Edinburgh, and colleagues. “Given the current paucity of diagnostic and prognostic biomarkers in these disorders, this result clearly indicates that further studies into its utility are warranted,” they added.
Accumulation of TDP-43 represents the most significant pathological finding in about 95% of ALS and 50% of FTD patients. Transformation and aggregation of TDP-43 in these diseases causes widespread neurotoxicity.
Discovery of TDP-43 along with evidence about the shared genetics of FTD and ALS have led researchers to consider them to be part of a single disease continuum. Both FTD and ALS are incurable, progressive, and fatal neurodegenerative diseases. FTD is the second most common cause of dementia after Alzheimer disease in people under age 65.
Currently no biomarkers exist for ALS or FTD, and diagnosis can prove challenging. Biomarkers could help in risk stratification, earlier treatment, and enrollment in clinical trials for drug development.
To evaluate evidence supporting TDP-43 as a biomarker for ALS and FTD, researchers searched seven databases without restriction to publication date or language. The analysis included 7 studies that evaluated TDP-43 in the cerebrospinal fluid (CSF) of 274 participants (150 controls, 94 with ALS, 77 with FTD).
Key results •Compared with controls, significantly higher levels of TDP-43 in: FTD-ALS spectrum disorder (FTD and ALS combined; p < 0.05) ALS alone (p = 0.02) •TDP-43 not significantly increased in FTD alone vs controls (p = 0.59)
The authors noted that the significant finding for ALS-FTD patients could have resulted if ALS patients were lumped in with FTD patients. Further studies are needed to confirm whether TDP-43 can be included as a biomarker in FTD, and whether levels of it increase with disease progression. Included studies varied in the methods they used and were limited by poor reporting of bias, although there was no evidence of publication bias.
Take home points •First systematic review and meta-analysis of its kind found that the RNA binding protein TDP-43 may be a promising new biomarker for diagnosing ALS •Further studies are needed to confirm the findings and evaluate whether TDP-43 levels increase with disease progression.