Towards a TDP-43-Based Biomarker for ALS and FTLD.
Emily FenebergElizabeth GrayOlaf AnsorgeKevin TalbotMartin R TurnerPublished in: Molecular neurobiology (2018)
TDP-43 accumulates in nerve cells of nearly all cases of amyotrophic lateral sclerosis (ALS; the commonest form of motor neuron disease) and in the majority of Tau-negative frontotemporal lobar degeneration (FTLD). There is currently no biochemical test or marker of disease activity for ALS or FTLD, and the clinical diagnosis depends on the opinion of an experienced neurologist. TDP-43 has a key role in the pathogenesis of ALS/FTLD. Measuring TDP-43 in easily accessible biofluids, such as blood or cerebrospinal fluid, might reduce diagnostic delay and offer a readout for use in future drug trials. However, attempts at measuring disease-specific forms of TDP-43 in peripheral biofluids of ALS and FTLD patients have not yielded consistent results, and only some of the pathological biochemical features of TDP-43 found in human brain tissue have been detected in clinical biofluids to date. Reflecting on the molecular pathology of TDP-43, this review provides a critical overview on biofluid studies and future directions to develop a TDP-43-based clinical biomarker for ALS and FTLD.
Keyphrases
- amyotrophic lateral sclerosis
- disease activity
- cerebrospinal fluid
- end stage renal disease
- rheumatoid arthritis
- systemic lupus erythematosus
- chronic kidney disease
- newly diagnosed
- induced apoptosis
- rheumatoid arthritis patients
- emergency department
- current status
- prognostic factors
- cell proliferation
- oxidative stress
- peritoneal dialysis
- juvenile idiopathic arthritis
- endoplasmic reticulum stress
- single molecule
- drug induced