Objective: To investigate whether 4R-TAU seed amplification assay discriminates tauopathies from non-tauopathies as well as CBD from PSP in post-mortem brain samples.
Background: 4 repeat tau (4R-TAU) protein aggregates within neurons and glial cells are the hallmarks of tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). These neurodegenerative disorders exhibit significant similarities among them and with other degenerative parkinsonisms in both clinical manifestations and pathological attributes. A definitive biomarker is an unmet need, but in recent years seed amplification assays (SAAs) have emerged as a promise.
Method: Here, we analyzed a set of 14 postmortem striatum tissue homogenates of control subjects (CSs, n=3) and patients with Parkinson’s disease (PD, n=3), multiple system atrophy (MSA, n=3), progressive supranuclear palsy (PSP, n=5), and corticobasal degeneration (CBD, n=3). Using a 4R-TAU SAA, we assessed: (i) whether the 4R-TAU SAA can differentiate tauopathies (PSP and CBD) from synucleinopathies (MSA and PD) and healthy controls (CSs); (ii) whether the 4R-TAU SAA can specifically discriminate CBD and PSP.
Results: The 4R-TAU SAA supported the clinical diagnosis with a sensitivity of 80% (4/5) for PSP and 100% (3/3) for CBD, with 100% specificity against control subjects (0/3). Compared to PSP, CBD samples exhibited higher seeding activity, characterized by a significantly shorter lag time (time to reach the threshold) (p<0.05) and T50 (time to achieve 50% of maximum ThT signal) (p < 0.05).
Conclusion: Our study suggests that TAU SAA effectively differentiates tauopathies from synucleinopathies. The preliminary, yet significant trend for 4R-TAU to discriminate successfully between CBD and PSP warrants further assessment in larger samples of postmortem tissue and more importantly in intravitam CSF.
Abstract previously presented at the Neuro2024: The PSP and CBD International Research Symposium, October 24 – 25, 2024, Toronto, Canada
To cite this abstract in AMA style:
L. de Mena, M. Fernandez, J. Perez, C. Painous, A. Camara, A. Perez-Soriano, L. Molina-Porcel, E. Artikis, B. Caughey, Y. Compta. 4R-TAU seed amplification assay discriminates tauopathies from non-tauopathies and CBD from PSP in post-mortem brain samples [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/4r-tau-seed-amplification-assay-discriminates-tauopathies-from-non-tauopathies-and-cbd-from-psp-in-post-mortem-brain-samples/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/4r-tau-seed-amplification-assay-discriminates-tauopathies-from-non-tauopathies-and-cbd-from-psp-in-post-mortem-brain-samples/