An ultra-sensitive test could improve dementia diagnosis by detecting protein clumps linked to rarer forms of cognitive decline.
The test targets abnormal clumps of TDP-43, a protein linked to a subtype of frontotemporal lobar degeneration.
Frontotemporal lobar degeneration, or FTLD, is a group of brain disorders that can affect behaviour, emotions, language and planning.
Investigators developed the test to detect FTLD-TDP, a specific form of FTLD marked by a build-up of abnormal TDP-43 protein.
The researchers said their findings could help doctors better identify the underlying disease process in dementia patients, while also supporting research and drug development.
“In this study, we found elevated concentrations of a biomarker that correlates with FTLD-TDP disease severity,” said co-senior author David R. Walt, PhD, of the Mass General Brigham department of pathology.
“This is just a first step, but it’s an important one because it gives us something measurable. Our vision is to create a test to diagnose patients, monitor treatment efficacy in clinical trials, and follow patient progression.”
Current biomarkers can help diagnose Alzheimer’s disease, but rarer dementia-related conditions, including FTLD and its subtypes, remain harder to identify.
Biomarkers are measurable signs in the body that can help show whether a disease is present or track how it is progressing.
Doctors currently use imaging tests to see whether the brain is degenerating, but these scans cannot always distinguish the molecular cause of FTLD.
To develop the biomarker test, researchers adapted an approach previously used to detect misfolded alpha-synuclein, a protein linked to Parkinson’s disease.
The digital seed amplification assay, or dSAA, divides a patient’s cerebrospinal fluid into tiny compartments and counts TDP-43 protein “seeds” under a microscope.
Cerebrospinal fluid is the clear fluid that surrounds the brain and spinal cord.
Researchers analysed 30 cerebrospinal fluid samples from people with FTLD-TDP and 10 from healthy controls.
People with FTLD-TDP had higher concentrations of TDP-43 seeds, and seed levels were linked to disease severity.
The more severe a patient’s symptoms, the more seeds the test detected.
Researchers said the findings suggest the test could help recruit patients more accurately for clinical trials and monitor treatment efficacy or disease progression over time.
However, the study was small, did not confirm FTLD-TDP diagnoses through autopsy and did not compare results with other types of dementia.
The researchers said larger studies involving different neurodegenerative diseases, long-term follow-up and autopsy-confirmed diagnoses are needed to validate the test.
Experts to push for four-day week after research links long hours working to obesity
