Diagnosing dementia with Lewy bodies (DLB) has long been one of neurology's more stubborn problems. The condition shares significant symptom overlap with Alzheimer's disease (AD) and other dementias, and misdiagnosis is common — with real consequences, since treatments effective for one condition can be harmful in another. A new study published in Nature Medicine may change that.
An international consortium led by researcher Katharina Bolsewig and neurologist Charlotte Teunissen at UMC and their team, has validated DOPA decarboxylase (DDC) as a promising cerebrospinal fluid (CSF) biomarker for both Parkinson's disease and DLB. DDC is an enzyme central to dopamine biosynthesis in the brain, and its elevation in CSF appears to reflect the dopaminergic neuron loss that characterizes DLB.
The team developed two novel DDC immunoassays and validated them across three clinical cohorts totaling 740 participants, as well as a biologically defined cohort, a cohort with dopamine transporter imaging data, and an autopsy-confirmed cohort — representing one of the most thorough validations of a neurodegeneration biomarker to date.
The results showed that CSF DDC levels were significantly elevated in patients with DLB and PD — up to 2.5 times higher than in healthy controls and nearly twice the levels seen in AD — with area-under-the-curve diagnostic values exceeding 0.9, indicating high discriminatory power. Critically, that separation from AD patients makes DDC a highly specific marker, not just a general signal of neurodegeneration.
This specificity matters clinically. DLB is the second most common form of degenerative dementia after AD, yet it remains widely underdiagnosed. Patients misidentified as having AD may be prescribed antipsychotic medications that can trigger severe, sometimes fatal reactions in DLB patients. An objective fluid-based test could catch misdiagnoses before they cause harm.
The study also found that elevated DDC levels correlated with the presence of motor impairment — a hallmark of Parkinson's disease — though not with its severity, suggesting the marker tracks disease presence more than progression. Earlier work published in Nature Aging had already indicated that CSF DDC can detect preclinical DLB stages in clinically unimpaired individuals and predict progression to clinical disease over a three-year period, adding a potential early-detection dimension to its utility.
One important nuance: a related Nature Communications study found that while CSF DDC has strong diagnostic potential, plasma DDC levels are heavily influenced by dopaminergic treatment, limiting its usefulness as a blood-based diagnostic — though it may still have value as a treatment-monitoring tool. For now, the strongest application remains in CSF testing.
The consortium emphasizes that further standardization of assay protocols across labs will be needed before the test enters routine clinical use. Still, the scale of validation here — spanning multiple independent cohorts and confirmed in autopsy tissue — places DDC among the most rigorously evidenced biomarker candidates in the neurodegenerative disease space.
