June 27, 2026

@michaelokun

Could a blood test help track tau pathology in BPAN? Tau is a protein that helps stabilize brain cells, and abnormal tau buildup is linked to several neurodegenerative diseases. Jae-Hyeok Lee and colleagues describe a new observation in Movement Disorders showing that plasma pTau217 levels were markedly elevated in children and adolescents w/ Beta-Propeller Protein-Associated Neurodegeneration (BPAN), a rare neurodegenerative disorder caused by WDR45 mutations. Key points: - All five genetically confirmed BPAN patients had plasma pTau217 levels that exceeded both Parkinson's disease controls and also healthy reference values. - The findings support previous pathology studies showing that BPAN is associated w/ substantial tau accumulation and neurofibrillary tangles. - Other neurodegeneration biomarkers including GFAP, NfL, and S100B were not significantly different between groups, suggesting pTau217 may provide unique biological information. My take: This small study raises an intriguing possibility. Could pTau217 become a useful blood biomarker for tracking tau pathology beyond Alzheimer's disease? BPAN is an ultra-rare disorder, however the biology may teach us important lessons about how abnormal tau accumulates in the human brain. The observation also highlights the growing power of blood biomarkers to reveal disease mechanisms that previously required neuropathology. Larger studies will be needed, but this is an exciting first step. Here are 5 points that resonated w/ me: 1- BPAN is increasingly being recognized as a tauopathy and not simply a disorder of brain iron accumulation. 2- Blood biomarkers may provide a window into disease biology even in rare pediatric neurodegenerative disorders. 3- Elevated pTau217 may reflect impaired autophagy and reduced clearance of abnormal tau proteins. 4- Understanding why pTau217 is elevated in BPAN may provide broader insights into tau related neurodegeneration. 5- The future may include blood based biomarkers that help diagnose, monitor, and eventually guide treatments for rare neurodegenerative diseases before substantial disability emerges. https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.70405