Although incidental Lewy body disease (ILBD) entails no clinical signs of Parkinson’s disease, researchers found that histologic markers of the midbrain in patients with ILBD are representative of premotor Parkinson’s disease.
HONOLULU—Analysis of neuronal density, tyrosine hydroxylase counts, and dopamine transporter levels in the brains of patients with incidental Lewy body disease (ILBD) suggests that the disease could be a preclinical form of Parkinson’s disease, according to a study presented at the 63rd Annual Meeting of the American Academy of Neurology.
Joshua M. Milber, a research technician from the Philadelphia Veteran Affairs Medical Center, and colleagues also tested the patients for ionized calcium binding adaptor molecule 1 (IBA-1) and found correlations between the two conditions.
“ILBD involves no clinical signs of Parkinson’s disease but significant Lewy pathology within the brain and may represent a preclinical phase of Parkinson’s disease,” the authors wrote. They analyzed the brains of 61 participants (15 healthy controls, 33 patients with ILBD, and 13 patients with Parkinson’s disease) to identify the histologic markers that characterize Parkinson’s disease midbrain, and to assess if ILBD could logically predicate Parkinson’s disease along its microscopic progression.
Comparing Neuronal Density in Parkinson’s Disease and ILBD
The investigators recorded the levels of neuronal density and tyrosine hydroxylase in the substantia nigra—an area in which cell loss has been shown to correlate with the presence of motor symptoms of Parkinson’s disease—of all patients, as well as dopamine transporter levels in the striatum.
Controls and patients with Parkinson’s disease had lower tyrosine hydroxylase–negative counts (5.18 and 1.76, respectively) and lower IBA-1 levels (4.11 and 4.33, respectively) than patients with ILBD. Patients with ILBD had higher neuronal density than patients with Parkinson’s disease and controls.
“There were positive correlations between nigral IBA-1 level and tyrosine hydroxylase–negative count and total neuronal count,” the researchers reported. Regarding the striatum, the researchers also found that total nigral neuronal density featured a positive trend with dopamine transporter levels. “Within ILBD, [tyrosine hydroxylase–negative counts] negatively correlated with both putamen dopamine transporter levels and caudate nucleus dopamine transporter levels,” they added.
A Potential Biomarker for Parkinson’s Disease
The study authors determined that ILBD is a condition pathologically distinct from Parkinson’s disease characterized by intermediate nigral neuronal density, significant nigral tyrosine hydroxylase downregulation, intermediate microglial activation, and intermediate striatal dopamine depletion. “Tyrosine hydroxylase production has been shown to be a valid marker for neuronal integrity,” they noted. “Moderate midbrain dopaminergic cell loss and dysfunction in ILBD cases would support the notion of ILBD as preclinical Parkinson’s disease.”
The results of this study also confirm the notion that microglia play a role in the early progression of Parkinson’s disease. “As the frequency of tyrosine hydroxylase–negative cells increases in the substantia nigra along Parkinson’s disease progression, the area occupied by activated microglia increases, as expected,” the investigators explained. “This may produce a protective and/or detrimental effect on functional cells.
“Although currently only available postmortem, these biomarkers may eventually serve reliably to determine which patients develop Parkinson’s disease later in life,” they concluded.
—Ariel Jones