Researchers at Mass General Brigham have developed an ultrasensitive test that detects abnormal clumps of TDP-43, the protein that defines a subtype of frontotemporal lobar degeneration known as FTLD-TDP. Writing in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, the team reported that concentrations of the biomarker were elevated and tracked with the severity of FTLD-TDP disease.
That matters because the diagnostic tools available today are lopsided. Biomarkers can identify Alzheimer's disease with increasing confidence, but rarer pathologies such as FTLD and its subtypes have no equivalent, leaving clinicians to infer the underlying pathology from symptoms alone. Dementia affects more than 57 million people worldwide, a figure projected to nearly double over the next two decades, and much of that burden comes from brain pathologies that current tests cannot distinguish.
Co-senior author David R. Walt of the Mass General Brigham Department of Pathology described the result as a first step that nonetheless gives researchers something measurable. The longer-term aim, he said, is a test that can diagnose patients, gauge whether treatments are working in clinical trials, and follow disease progression over time - functions that are difficult to perform when the pathology itself is invisible to testing.
The investigators are clear that the test needs rigorous validation before it could be used in practice, and they note it is one of several efforts underway internationally to give frontotemporal dementia patients an accurate diagnosis. That accuracy is not an academic point: drug development for FTLD depends on being able to enroll the right patients and measure whether a therapy is changing the underlying molecular pathology.