pTau181 biomarker now TGA approved – what does that mean?

13th August 2026, A/Prof Chee L Khoo

is there beta-amyloid in there?

We know (maybe better phrased – we think we know) that it is the amyloid-β (Aβ) plaques that are a key driver of pathological processes in Alzheimer’s disease (AD) (1,2).  Targeting the Aβ should then prevent or at the very least delay the progression of the dementia. The problem with prevention is that we don’t know who are going to get dementia till there is some cognitive impairment. Many patients have high risk factors for dementia but we still can’t treat them till there is some cognitive impairment. Aβ positivity has been estimated to precede clinical disease onset by 20–30 years (3). Aβ accumulation may thus already approach a plateau within preclinical disease stages. (4-6).  Thus, we depend on the biomarkers that accurately predict amyloid-β accumulation and hence, tells us who may be at risk of getting dementia. Where does pTau181 sit and how does that help us with the patient in front of us?

Tau is a protein that stabilises microtubules in neurons, essential for intracellular transport and neuronal health. In AD, tau becomes abnormally phosphorylated, particularly at threonine 181, which reduces its ability to bind microtubules. This leads to tau detachment, aggregation, and formation of neurofibrillary tangles, a hallmark of AD pathology. Phosphorylated tau 181 and phosphorylated tau 217 (pTau181 and pTau217) are some of the key biomarkers in AD and can be measured either in the CSF or plasma. Plasma levels correlate well with CSF levels.

Plasma tau phosphorylated at threonine 181 and 217 can discriminate clinically diagnosed AD dementia from both other neurodegenerative diseases and cognitively normal individuals (7-11). Further, levels of plasma p‐tau181is associated with AD disease severity, predict brain amyloid and tau pathology captured by PET imaging, and predict AD pathology on autopsy (12,13).

By detecting early AD and predict future preclinical Aβ accumulation, could identify clinical trial candidates in whom the efficacy of therapies in inhibiting or preventing Aβ accumulation can be assessed before any cognitive impairment is present.

In the longitudinal cohort study, Finish Prevent Alzheimer’s Disease Cohort (F-PACK), baseline plasma pTau181, pTau217 and amyloid-β PET load were used to predict future amyloid-β accumulation in 75 asymptomatic elderly. Both pTau181 and pTau217 were able to identify CU elderly in whom Aβ load will subsequently increase across a median time period of 5 years (range 2–10 years), and this is regardless of their Aβ PET status at baseline (14). Plasma pTau181, pTau217 and Aβ PET load correlated similarly with longitudinal Aβ rate of change, and when combined in a multimodal biomarker model, all three biomarkers lost their individual predictive abilities, implying strong collinearity.

Tropea, T et al. also demonstrated that plasma p‐tau181 differentiates AD pathology cases from NC with high accuracy (15). Higher levels of plasma p‐tau181 are associated with faster cognitive and functional decline. There have been numerous studies confirming the utility of using these biomarkers in “confirming” AD and tracking progression. Hence, the approval from FDA and TGA recently.

At least, these biomarkers help identify patients with early disease before MCI but does current treatment help to prevent or slow down progression remains to be seen. There is still some agreement needed to ascertain what is an optimal cut off point for diagnosis. Further, different pTau181 assays used in different clinical trials and they are not all the same. My understanding is that the TGA approved assay is the Roche Elecsys® system (16).

  While we wait for clinical data to arrive, there are lots we can do to mitigate against progression – managing risk factors such as blood pressure, lipids, glucose, wholesome diet and lifestyle measures including resistance exercises.

References:

  1. Hardy JA, Higgins GA. Alzheimer’s disease: The amyloid cascade hypothesis. Science. 1992;256(5054):184–185.
  2. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature. 1999;399(6738 Suppl):A23–A31
  3. Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA. 2015;313(19):1924–1938
  4. Jack CR, Wiste HJ, Lesnick TG, et al. Brain β-amyloid load approaches a plateau. Neurology. 2013;80(10):890–896. 
  5. Villemagne VL, Burnham S, Bourgeat P, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol. 2013;12(4):357–367. 
  6. Buchhave P, Minthon L, Zetterberg H, et al. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69(1):98–106.
  7. Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative accuracy of plasma Phospho‐tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772‐781. 
  8. Ashton NJ, Pascoal TA, Karikari TK, et al. Plasma p‐tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021;141(5):709‐724. 
  9. De Meyer S, Vanbrabant J, Schaeverbeke JM, et al. Phospho‐specific plasma p‐tau181 assay detects clinical as well as asymptomatic Alzheimer’s disease. Ann Clin Transl Neurol. 2022;9(5):734‐746. 
  10. Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P‐tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat Med. 2020;26:379‐386. 
  11. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19(5):422‐433
  12. Lantero Rodriguez J, Karikari TK, Suárez‐Calvet M, et al. Plasma p‐tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post‐mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol. 2020;140(3):267‐278. 
  13. Mielke MM, Hagen CE, Xu J, et al. Plasma phospho‐tau181 increases with Alzheimer’s disease clinical severity and is associated with tau‐ and amyloid‐positron emission tomography. Alzheimers Dement. 2018;14(8):989‐997
  14. De Meyer S, Schaeverbeke JM, Luckett ES, Reinartz M, Blujdea ER, Cleynen I, Dupont P, Van Laere K, Vanbrabant J, Stoops E, Vanmechelen E, di Molfetta G, Zetterberg H, Ashton NJ, Teunissen CE, Poesen K, Vandenberghe R. Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid PET. Brain Commun. 2024 May 23;6(4):fcae162
  15. Tropea TF, Waligorska T, Xie SX, Nasrallah IM, Cousins KAQ, Trojanowski JQ, Grossman M, Irwin DJ, Weintraub D, Lee EB, Wolk DA, Chen-Plotkin AS, Shaw LM; Alzheimer’s Disease Neuroimaging Initiative. Plasma phosphorylated tau181 predicts cognitive and functional decline. Ann Clin Transl Neurol. 2023 Jan;10(1):18-31
  16. https://florey.edu.au/wp-content/uploads/2025/10/3.-MC-AU-04079-External-MC-AU-04079-Availability-of-pTau181-plasma-Announcement.pdf Accessed 13/08/2026