Objective: To report three cases of progressive supranuclear palsy (PSP) with significantly elevated pTau-181 levels on serum testing.

Background: According to the MDS-endorsed PSP Study Group, PSP patients can present with a wide range of phenotypes.  These include oculomotor dysfunction, postural instability, parkinsonism, behavioral variant frontotemporal dementia, progressive gait freezing, corticobasal syndrome, primary lateral sclerosis, cerebellar ataxia, non fluent/agrammatic primary progressive aphasia and progressive apraxia of speech1.  Patients with atypical presentations other than the classical Richardson’s syndrome accounted for 76% of autopsy confirmed PSP cases according to this study group1.

Method: Routine history taking and a neurological examination revealed three patients with clinical signs of PSP per the MDS-PSP criteria.  A serum ATN profile measuring beta amyloid 42, beta amyloid 40, phosphorylated Tau-181 (pTau-181), and neurofilament light chain levels (NfL) was ordered for these patients as they were also experiencing symptoms of episodic memory loss.

Results:

An 84 yo woman with presumed tremor predominant Parkinson’s disease was found to have a normal b-amyloid 42/40 ratio of 0.106 pg/mL (N > 0.102), elevated pTau-181 of 2.96 pg/mL (N < 0.97), and an elevated neurofilament light chain level of 15.10 pg/mL (N <3.65).  A 73 yo woman presented with bvFTD followed by apraxia of speech, postural instability, oculomotor dysfunction, and diffuse dystonia.  Her ATN profile showed a b-amyloid 42/40 ratio of 0.115 pg/mL, a pTau-181 level of 1.38 pg/mL, and elevated neurofilament light chains of 10.80 pg/mL.  Lastly, an 83 year old man with progressive spastic dysarthria and findings of acute on chronic neurogenic changes in the cervical and lumbar regions, was found to have a normal b-amyloid 42/40 ratio of 0.108 pg/mL, elevated pTau-181 of 2.01 pg/mL, and elevated neurofilament light chain levels of 13.30 pg/mL.

Conclusion: The pTau-181 serum biomarker was elevated in three PSP phenotypes (parkinsonism, predominant frontal, and primary lateral sclerosis).  Zheng et al determined that an elevated pTau-181 could differentiate PSP patients from healthy controls and patients with Parkinson’s disease.  I believe that this serum biomarker may also be able to detect atypical presentations of PSP, and could lead to rapid diagnosis of these complicated, often underdiagnosed patients.

References: Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, Mollenhauer B, Müller U, Nilsson C, Whitwell JL, Arzberger T, Englund E, Gelpi E, Giese A, Irwin DJ, Meissner WG, Pantelyat A, Rajput A, van Swieten JC, Troakes C, Antonini A, Bhatia KP, Bordelon Y, Compta Y, Corvol JC, Colosimo C, Dickson DW, Dodel R, Ferguson L, Grossman M, Kassubek J, Krismer F, Levin J, Lorenzl S, Morris HR, Nestor P, Oertel WH, Poewe W, Rabinovici G, Rowe JB, Schellenberg GD, Seppi K, van Eimeren T, Wenning GK, Boxer AL, Golbe LI, Litvan I; Movement Disorder Society-endorsed PSP Study Group. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017 Jun;32(6):853-864. doi: 10.1002/mds.26987. Epub 2017 May 3. PMID: 28467028; PMCID: PMC5516529
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, Hampel H, Jagust WJ, Johnson KA, Knopman DS, Petersen RC, Scheltens P, Sperling RA, Dubois B. A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016 Aug 2;87(5):539-47. doi: 10.1212/WNL.0000000000002923. Epub 2016 Jul 1. PMID: 27371494; PMCID: PMC4970664.
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 March 13, 2026.

S. Ghourchian, A. Kay. A Case of Mixed Presentation of 4R Tauopathies [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/a-case-of-mixed-presentation-of-4r-tauopathies/. Accessed March 13, 2026.
YC. Zheng, HH. Cai, WY. Kou, ZW. Yu, T. Feng. Plasma tau-species-containing neuron-derived extracellular vesicles as potential biomarkers for progressive supranuclear palsy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/plasma-tau-species-containing-neuron-derived-extracellular-vesicles-as-potential-biomarkers-for-progressive-supranuclear-palsy/. Accessed March 15, 2026.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/an-elevation-in-the-serum-biomarker-ptau-181-may-identify-progressive-supranuclear-palsy-pathology/