Objective: To evaluate plasma phosphorylated tau at threonine 217 (pTau217) and neuromelanin-sensitive MRI (NM-MRI) as candidate biomarkers reflecting tau pathology and nigral iron deposition in pediatric patients with BPAN.

Background: BPAN is a rare subtype of neurodegeneration with brain iron accumulation (NBIA) caused by WDR45 mutations. Previous neuropathological studies have reported widespread hyperphosphorylated tau in affected patients, but no blood-based biomarker has been established for this tau pathology. In addition, the nigral “halo sign” on T1-weighted MRI, which is considered pathognomonic for BPAN, is often not clearly visible in pediatric patients.

Method: Five pediatric patients (age range: 2–16 years) with genetically confirmed WDR45 mutations were included. Plasma pTau217 was measured in all five patients using a proximity extension assay-based proteomics panel, and the results were compared with those of 32 Parkinson’s disease (PD) patients and published normative data from healthy adults. In three patients with available MRI data (ages 9, 12, and 15 years), NM-MRI was compared with conventional T1-weighted sequences at 3 Tesla. Abstract writing was assisted by an AI language tool; all data and conclusions were verified by the authors.

Results: Plasma pTau217 levels were elevated in all five BPAN patients compared to PD controls, and all patients exceeded the 90th percentile of healthy adult normative values, with the highest level observed in the oldest patient. On susceptibility-weighted imaging (SWI), nigral hypointensity was observed in all three patients. Conventional T1-weighted sequences did not show the halo sign in any patient. In contrast, NM-MRI clearly showed the halo sign in the two older patients, while the result was indeterminate in the youngest patient.

Conclusion: Elevated plasma pTau217 in all BPAN patients suggests that tau accumulation is driven by disease pathology, possibly via impaired autophagy-mediated tau clearance. NM-MRI was more useful than conventional T1-weighted sequences for visualization of the halo sign, although its detectability appeared to be age-dependent. These two candidate biomarkers reflect different aspects of BPAN pathology, and further studies combining both markers may help establish a non-invasive diagnostic framework for this rare disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-phospho-tau217-and-neuromelanin-sensitive-mri-as-candidate-biomarkers-in-beta-propeller-protein-associated-neurodegeneration/