HAI Book 2025 - Flipbook - Page 727
Ferreira, Pamela
Head-to-head association of plasma p-tau217 with MK6240, Flortaucipir,
PI2620, and RO948 Tau PET Tracers
Pamela C L Ferreira1, Bruna Bellaver1, Guilerme Povala1, Guilherme Bauer-Negrini1, Firoza
Lussier1, Andreia Rocha1, Emma Ruppert1, Carolina Soares1, Livia Amaral1, Rayan Mroue1,
Cynthia Felix1, Joseph Masdeu2, Dana L. Tudorascu1, Belen Pascual2, Brian Gordon3, Val
Lowe4, Hwamee Oh5, David Soleimani-Meigooni6, Juan Fortea7, Pedro Rosa-Neto8, Suzanne
Baker9, Tharick A. Pascoal1
1
University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, US
Houston Methodist Research Institute, Department of Neurology, Houston, TX, US
3
Washington University in St. Louis, Department of Radiology, St. Louis, MO, US
4
Mayo Clinic, Department of Radiology, Rochster, MN, US
5
Brown University, Department of Psychiatry and Human Behavior, Providence, RI, US
6
University of California San Francisco, Memory and Aging Center, San Francisco, CA, US
7
Hospital de la Santa Creu i Sant Pau, Sant Pau Memory Unit, Department of Neurology, Barcelona, ES
8
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research
Institute, Montréal, QC, CA
9
Lawrence Berkeley National Laboratory, Berkeley, CA, US
2
Background: Tau phosphorylation and aggregation are hallmark features of Alzheimer's disease pathology(AD).
Previous studies have shown that plasma phosphorylated tau (p-tau) at threonine 217 is associated with tau tangle
PET pathology. However, the comparative strength of the association between p-tau217 and different tau PET
tracers remains unexplored. Here, we conducted a head-to-head comparison of the association between plasma
p-tau217 and four distinct tau PET tracers.
Methods: We studied 330 individuals across the AD continuum from the HEAD study[187 cognitively unimpaired
elderly(CU), 104 with mild cognitive impairment(MCI), and 39 with dementia] with available Flortaucipir, MK6240,
A´ PET, and plasma p-tau217 data. A subset of 63 individuals(26 CU, 25 MCI, and 12 dementia) also had PI2620 and
RO948. PET stages were defined similarly to recent proposals by the AA working group. The magnitude of the
association was determined using significant ´ values from regression models testing the association between
each tau PET tracer and plasma p-tau217, and the extent was measured by the percentage of significantly
abnormal voxels(t-value>3.2) in each region.
Results:We found that plasma p-tau217 levels significantly increased across all PET disease stages for MK6240,
whereas no significant difference was observed between low and intermediate stages for Flortaucipir(Figure 1). In
CU individuals, the magnitude of the association with plasma p-tau217 was higher for MK6240 compared to
Flortaucipir(Figure 2A-C). The extent of the association was also greater for MK6240, particularly in early Braak
regions(Figure 2D). In CI individuals, the magnitude of the association was higher for MK6240, whereas the extent
was similar for MK6240 and Flortaucipir. Using the subset of individuals who had the four tau tracers, MK6240
showed a stronger overall association with p-tau217, followed by PI2620, RO948 and Flortaucipir(Figure 3).
Conclusion: Overall, our results indicate that the four tau PET tracers exhibit robust associations with plasma ptau217 in similar topographical regions.
HAI2025 - 727
