CSF biomarker associated with abnormal accumulation of TAR DNA-binding protein 43, to identify amyotrophic lateral sclerosis (ALS) and the most common form of frontotemporal lobar degeneration (FTLD-TDP) in patients.
- Offers a diagnosis that does not rely on physician observation of patient's symptoms.
- Provides high sensitivity and specificity for the detection of ALS and FTLD-TDP.
ALS is the most common cause of progressive weakness, and FTLD is the second most common cause of progressive dementia among those under the age of 65. Because ALS is phenotypically similar to several other neurological diseases, its clinical diagnosis can be challenging. Similar brain changes have been found in ALS and FTLD with TDP-43 accumulation (FTLD-TDP), and treatments for both ALS and FTLD-TDP are often delayed because of similarities between these diseases and other types of peripheral nerve disease and FTLD. Currently, there is neither a test that can provide a definite diagnosis of ALS nor a reliable biomarker that can detect FTLD-TDP or ALS early in the course of either disease.
Frontotemporal lobar degeneration (FTLD) is the pathological term for the clinical syndrome frontotemporal dementia, a group of conditions resulting from the progressive degeneration of the temporal and frontal lobes of the brain. Pathologically, two main causes of FTLD have been identified, FTLD associated with TAR DNA binding protein (FTLD-TDP) and FTLD associated with Tau (FTLD-Tau). FTLD-TDP and FTLD-Tau can each lead to clinical syndromes with prominent behavioral or language changes. In particular, amyotrophic lateral sclerosis (ALS) shares the pathologic changes of FTLD-TDP, while other dementias and aphasias share the pathologic changes of FTLD-Tau.
Using cerebrospinal fluid collected from patients with FTLD-TDP and FTLD-Tau, Emory researchers have found that the ratio of a specific phosphorylated tau to total detectable tau is much lower in FTLD-TDP patients than FTLD-Tau patients and control subjects. Using this ratio as a predictive biomarker of FTLD-TDP, they can distinguish between FTLD-TDP and FTLD-Tau with 82% sensitivity and 89% specificity. The use of this CSF biomarker will significantly improve the cliniciansÃ¢â‚¬â„¢ ability to distinguish between FTLD-TDP and FTLD-Tau early in the disease course and enhance the design of clinical trials targeting FTLD-TDP and FTLD-Tau. This biomarker will also enable ALS detection early in the disease course which will allow early intervention.
Biomarker has been identified and can be distinguished from Tau with 82% sensitivity and 89% specificity.